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Stem cells & regeneration: 644 3D models

Pluripotent and adult stem cells, niches, differentiation, organoids and stem cell therapy (real sizes µm–cm). Each one is a ready-made 3D model you can turn, recolour and place in a figure — open BioDiorama and type its name in the Library search.

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Pluripotent cells · Colonies & culture · Embryo origins · Concepts & history · Reprogramming · Epigenetic resetting · Pluripotency network & signalling · Naive & primed states · Embryoid bodies & germ layers · Teratomas & chimaeras · Gastruloids & germ cells · Blood & bone marrow · Intestine & oesophagus · Skin, hair & nail · Skeletal muscle · Brain & spinal cord · Mesenchymal & skeletal · Eye · Breast, prostate & glands · Germline stem cells · Liver & pancreas · Lung & airway · Teeth · Heart, kidney & other organs · Niche principles & behaviour · Model organisms · Lineage trees · Maturation sequences · Directed differentiation protocols · Stem-cell-derived cells · Transdifferentiation (direct conversion) · Dedifferentiation and plasticity · Fate landscapes and decisions · Fate cues and readouts · Gut & stomach organoids · Brain, eye & ear organoids · Kidney & bladder organoids · Liver & pancreas organoids · Lung & airway organoids · Gland & reproductive organoids · Skin, hair, tooth & lens organoids · Heart, muscle, bone & fat models · Blood-vessel & immune organoids · Stem-cell embryo models · Domes, spheroids & culture formats · Air–liquid interface & barrier models · Organ-on-chip with stem-cell-derived cells · Bioprinted & engineered constructs · Imaging & analysis of organoids · Disease models in organoids · Haematopoietic stem cell transplant · Cord blood banking & donation · Gene-modified & engineered cells · Mesenchymal stromal cell therapy · Cell therapy for the eye · Cell therapy for the brain & spinal cord · Cell therapy for the heart · Regenerative therapies for other organs · Cell manufacturing, testing & cryopreservation · Regeneration models · Transplant & cell therapy in the clinic · Tissue engineering bioreactors

Pluripotent cells 11

Pluripotent stem cell at a colony edge, cut open — A packed colony edge with one cell sliced through: a large nucleus with open chromatin and big nucleoli fills most of the cell; the thin rim of cytoplasm holds free ribosomes, a little ER, a small Golgi and a few small, round mitochondria, with microvilli and tight junctions at the top. (cell ≈ 12 µm)
Dissociated stem cell: blebbing and ROCK inhibitor — A human pluripotent stem cell on its own after dissociation: without cell contacts ROCK–myosin overactivates and the cell blebs and may die (anoikis); a ROCK inhibitor such as Y-27632 lets it spread and survive. (≈ 10–20 µm)
Pluripotency surface markers — A close-up of a colony's top surface: the domed apical membranes of neighbouring cells carry glycolipid antigens (SSEA-3, SSEA-4; SSEA-1 in mouse), keratan-sulfate epitopes TRA-1-60 and TRA-1-81 on the mucin podocalyxin, and CD9, EpCAM and E-cadherin. (≈ 12 µm (markers enlarged))
2C-like cell (totipotent-like) — About one in a hundred mouse ES cells passes through a 2-cell-embryo-like state: MERVL and Zscan4 switch on, chromocentres disperse and nucleoli look immature. Shown in a colony seen from above. (colony ≈ 90 µm)
Primordial germ cell–like cell (PGCLC) — A germ cell made from pluripotent stem cells: large and round with a clear cytoplasm, a big round nucleus, germ granules (nuage) around it and pseudopodia for migration. Marked by BLIMP1, TFAP2C, SOX17 (human) or STELLA (mouse). (≈ 12–15 µm)
XEN cells (extra-embryonic endoderm stem cells) — Stem cells of the primitive endoderm: they never form compact colonies but grow as scattered round, refractile cells and stellate, migratory cells (GATA4, GATA6, SOX17, PDGFRα). (field ≈ 90 µm)
Trophoblast stem cell colony — Trophoblast stem cells (TSCs) grow as flat epithelial colonies with sharp edges; when they differentiate, huge trophoblast giant cells with polyploid nuclei or multinucleate syncytiotrophoblast appear. (colony ≈ 150 µm)
Short G1: the pluripotent cell cycle — Pluripotent stem cells divide fast with a very short G1 phase and spend most of the cycle in S phase; somatic cells have a long G1. Arcs show the share of each phase. (diagram)
Fibroblast vs iPSC: size and shape — A spread dermal fibroblast is about ten times longer than a pluripotent stem cell; iPSCs are small, packed and almost all nucleus. 20 µm scale bar. (field ≈ 150 µm)
Mitochondria and metabolism: somatic vs pluripotent — Somatic cells have long, branched mitochondria and burn glucose by oxidative phosphorylation; pluripotent cells have few small, round mitochondria and turn most glucose into lactate. Reprogramming flips this switch early. (≈ 10–30 µm)
Haploid ES cells — ES cells from parthenogenetic or androgenetic embryos carry a single set of chromosomes, ideal for genetic screens; they slowly become diploid in culture, seen as the 1n peak shrinking. (nuclei ≈ 10 µm)

Colonies & culture 21

Human PSC colony on a matrix — A healthy colony of human embryonic or induced pluripotent stem cells: tightly packed small cells with large nuclei and a sharp, bright edge, on a basement-membrane matrix, laminin or vitronectin coat. (colony ≈ 150–250 µm)
Human ES colony on feeder cells — The classic culture: a thick, compact ES colony with a bright refractile border sits on a lawn of mitotically inactivated mouse embryonic fibroblasts (MEFs) or human foreskin fibroblasts. (colony ≈ 150 µm)
Mouse ES colonies (domed) — Mouse embryonic stem cells grow as small, shiny, three-dimensional domes whose cell borders are hard to see. In 2i/LIF they are round and uniform; in serum/LIF some colonies flatten and differentiate. (colonies ≈ 50–90 µm)
Colony quality: good, borderline, differentiated — How a colony looks tells its state: compact with a sharp edge (good), ragged with loosening edge cells (borderline), or a small core in a skirt of large flat cells (differentiated — remove it). (≈ 400 µm)
PSC colony in cross-section — A colony cut open: pluripotent stem cells form a tall, tightly packed epithelium with tight junctions (ZO-1) at the top, E-cadherin along the sides, nuclei in the middle and a contractile actin fence around the colony edge. (section ≈ 150 µm long)
Passaging stem cells — Lifting colonies for passaging: EDTA gives small clumps, collagenase or dispase lifts sheet fragments, Accutase or TrypLE gives single cells (with a ROCK inhibitor). Part of the colony stays on the dish. (field ≈ 240 µm)
Manual passaging: cutting a colony — The colony is cut into a grid of small squares with a pulled glass needle (or a passaging roller) and the pieces are lifted off and moved to a new dish. (colony ≈ 200 µm)
Picking a colony with a pipette tip — Under the stereo microscope a colony is scraped and drawn into a 200 µL pipette tip to start or clean a line — for example picking a new iPSC clone. (colony ≈ 250 µm)
Alkaline phosphatase–stained colonies — Pluripotent colonies stain red-purple for alkaline phosphatase; counting them in a reprogramming dish measures efficiency (often well under 1 %). (6-well plate (128 × 86 mm) or 10-cm dish)
Pluripotency immunofluorescence — A colony stained for pluripotency markers as seen down a fluorescence microscope: OCT4, NANOG or SOX2 in the nuclei, TRA-1-60 or SSEA-4 on the cell surface and DNA in every cell. (field ≈ 220 µm)
Colony growth over five days — From a few cells to a large, thick colony in five days: pluripotent stem cells double about every 16–24 hours and the colony centre grows thicker. (≈ 420 µm)
Single-cell cloning — One cell is placed in a well (by dilution, sorting or picking) and grows into a clonal colony — the way edited or reporter lines are made. (wells ≈ 0.3 mm field)
Cell competition in a colony — Within a colony, cells with low MYC or high p53 lose: they are squeezed out of the epithelium and die on top of it, so fitter cells take over. (colony ≈ 160 µm)
Culture-acquired chromosome changes — Long-term culture selects for recurrent gains that help cells grow: amplification of 20q11.21 (BCL2L1), trisomy 12 or 17, or an extra X. Shown as banded chromosomes. (diagram)
Pluripotency gene scorecard — A qPCR scorecard as a heat map: pluripotent samples are high for self-renewal genes and low for lineage genes; embryoid bodies switch on ectoderm, mesoderm and endoderm genes. (diagram)
Flow cytometry for pluripotency markers — A dot plot of SSEA-4 against TRA-1-60: a good culture has well over 90 % double-positive cells. (diagram)
Phase-contrast view of a colony — How a colony looks down a phase-contrast microscope: tightly packed grey cells with dark, prominent nucleoli and a bright halo along a sharp edge; differentiated cells look large and flat. (field ≈ 220 µm)
Confocal z-stack of a colony — Optical sections through an immunostained colony, pulled apart: OCT4-positive nuclei on every plane, the colony widest at mid-height. (colony ≈ 100 µm)
Multicolour clonal mosaic — Lineage tracing with a multicolour (Confetti-type) reporter: each cell's descendants keep its colour, so a colony is a mosaic of clonal patches. (colony ≈ 160 µm)
Nucleofection of stem cells — Electroporation puts plasmids, mRNA or Cas9 RNPs into stem cells: a pulse across the cuvette's aluminium plates opens brief pores in the membranes. (cuvette ≈ 12 mm wide)
What is in a stem cell medium (E8) — A defined medium for human PSCs needs only eight things: a DMEM/F12 base, insulin, selenium, transferrin, ascorbic acid, FGF2, TGF-β1 and bicarbonate. (bottle ≈ 13 cm)

Embryo origins 12

Human blastocyst (day 6), cut open — Where embryonic stem cells come from: a day-6 human blastocyst with its zona, an outer trophectoderm, a fluid-filled cavity and the inner cell mass split into epiblast and hypoblast. (≈ 150–200 µm)
Hatching blastocyst — Before it can implant, the expanded blastocyst squeezes out through an opening in its zona pellucida. (≈ 200 µm)
Inner cell mass: epiblast and primitive endoderm sorting — In the mouse ICM, NANOG (epiblast) and GATA6 (primitive endoderm) cells first form a salt-and-pepper mix (E3.5) and then sort, the primitive endoderm lining the cavity by E4.5. Seen from the cavity. (≈ 60 µm)
Compaction and polarity (8–16-cell embryo) — At the 8-cell stage blastomeres flatten against each other and form an apical domain on their outer face; at 16 cells outer cells keep YAP in the nucleus (trophectoderm) and inner cells do not (inner cell mass). (≈ 100 µm)
Isolating the inner cell mass — To derive ES cells the trophectoderm is removed: by immunosurgery (antibodies and complement lyse the outer cells), by laser, or by cutting with fine needles. (≈ 150 µm)
ICM outgrowth (ES cell derivation) — A blastocyst plated on feeders attaches, its trophoblast spreads as huge flat cells and the inner cell mass grows into a clump that is picked to start an ES cell line. (≈ 300 µm)
Deriving an ES cell line, step by step — From a donated embryo to a cell line: blastocyst, isolated inner cell mass, plated on feeders, outgrowth, first ES colonies. (diagram)
Single-blastomere biopsy — One cell is taken from an 8-cell embryo through a hole in the zona while a holding pipette steadies it — the embryo-sparing way to derive ES cells (and the method of preimplantation genetic testing). (≈ 100 µm)
Epiblast rosette and lumen — Around implantation the epiblast polarises into a rosette whose apical sides meet in the middle and open a lumen (the pro-amniotic cavity). Human PSCs in 3D gel form the same polarised cysts. (≈ 30–50 µm)
Germ cell specification in the epiblast — In the mouse egg cylinder, BMP4 from the extra-embryonic ectoderm induces a few proximal posterior epiblast cells to become primordial germ cells (BLIMP1, PRDM14, AP2γ), which cluster at the base of the allantois. (≈ 300 µm)
How the blastocyst fills with fluid — Trophectoderm cells pump sodium into the cavity with Na+/K+-ATPase on their inner side, water follows through aquaporins, and tight junctions keep it from leaking out. (strip ≈ 70 µm)
Blastocyst grading — Embryos are graded by expansion (1–6) and by the quality of the inner cell mass and trophectoderm (A–C): a hatching 5AA, an expanded 4BB and an early 2CC with few cells. (≈ 100–200 µm)

Concepts & history 8

Early lineage decisions — The first two decisions of mammalian development: outer trophectoderm vs inner cell mass, then epiblast (the source of ES cells and the embryo) vs hypoblast. (diagram)
Levels of potency — A staircase from totipotent (embryo and placenta) through pluripotent (all body cells) and multipotent to oligopotent and unipotent stem cells; each makes fewer kinds of cells. (diagram)
Blastomere separation (totipotency test) — Separating the two cells of a 2-cell embryo: each can still make a complete blastocyst — the cells are totipotent (as identical twins arise). (diagram)
Milestones in pluripotency research — From frog cloning (1962) and mouse ES cells (1981) through Dolly (1996), human ES cells (1998) and iPSCs (2006–2007) to human nuclear-transfer ES cells (2013) and the first iPSC-derived transplant (2014). (timeline)
What iPSCs are used for — iPSC lines feed disease modelling, drug screening, cell therapy and toxicology tests (for example heart-cell safety). (diagram)
Self-renewal or differentiation — Each division a stem cell either copies itself (self-renewal) or gives a daughter that starts to differentiate. (diagram)
Kinds of pluripotent stem cells — Pluripotent lines come from five routes: the embryo (ES), reprogrammed somatic cells (iPS), nuclear transfer (NT-ES), primordial germ cells (EG) and teratocarcinomas (EC). (diagram)
How pluripotency is tested — From least to most stringent: marker staining, embryoid bodies, teratomas, chimaeras, germline transmission and tetraploid complementation (human cells stop at teratomas). (diagram)

Reprogramming 28

Yamanaka factors opening chromatin — OCT4, SOX2 and KLF4 act as pioneer factors: they bind their motifs even on nucleosomes in closed chromatin, recruit remodellers and open it; c-MYC then binds open DNA and boosts transcription. (nucleosomes ≈ 11 nm)
Retroviral delivery of the four factors — The original method (Takahashi & Yamanaka, 2006): four retroviruses each carry one factor gene into a fibroblast and integrate it into the genome; the transgenes are silenced once the cell becomes pluripotent. (cell ≈ 60 µm)
Reprogramming vectors (gene cassettes) — How the factors are packed: a single polycistronic cassette linked by 2A peptides (STEMCCA, excisable with Cre at loxP), a doxycycline-inducible tet-on system, or a piggyBac transposon that can later be removed seamlessly. (diagram)
Sendai virus reprogramming — A non-integrating RNA virus: Sendai virions fuse with the cell membrane and release their RNA genome, which stays in the cytoplasm making the factors and is diluted out as cells divide. (virions ≈ 150–250 nm)
Episomal plasmid reprogramming — oriP/EBNA1 plasmids carrying the factors replicate once per cell cycle while tethered to chromosomes by EBNA1, then are gradually lost — leaving footprint-free iPSCs. (nucleus ≈ 18 µm)
Modified mRNA reprogramming — Daily transfection of chemically modified mRNAs (with a 5′ cap and poly(A) tail) in lipid particles: ribosomes translate them straight into the four factors, without DNA ever entering the cell. (scene ≈ 300 nm)
Reprogramming timeline (days 0–24) — Fibroblasts become iPSCs over three to four weeks: rapid division and rounding, mesenchymal-to-epithelial transition into small foci, early colonies expressing SSEA-4 and TRA-1-60, then mature colonies with sharp edges. With small molecules alone, cells pass through a XEN-like epithelial stage instead. (≈ 400 µm)
Mesenchymal-to-epithelial transition (MET) — An early step of reprogramming: spindle-shaped fibroblasts lose SNAIL and N-cadherin, switch on E-cadherin and EpCAM and pack into epithelial clusters joined by adherens junctions. (≈ 150 µm)
Picking the right iPSC colony — A reprogramming dish holds fully reprogrammed iPSC colonies (compact, sharp-edged, TRA-1-60 positive) among flat, granular partially reprogrammed colonies, piled-up transformed foci and leftover fibroblasts. (≈ 260 µm)
Surface markers along the reprogramming path — Cells lose fibroblast markers (CD44, CD13, THY1) and gain SSEA-4, then TRA-1-60 and TRA-1-81 as they round up and become pluripotent — the basis for sorting intermediates. (≈ 70 µm)
Barriers to reprogramming: senescence and p53 — Most cells never make it: the factors trigger p53/p21 and p16, so many cells senesce (large, flat, SA-β-gal positive) or die. Lowering p53 lets more colonies form. (≈ 240 µm)
Partial reprogramming (rejuvenation) — Short, repeated pulses of OSK reset signs of ageing — DNA damage foci, lipofuscin, swollen mitochondria, an old epigenetic age — without the cell losing its identity. (≈ 80 µm cells)
Reprogramming on the epigenetic landscape — Waddington's landscape run backwards: reprogramming pushes a somatic cell out of its valley, over epigenetic barriers and back up to the pluripotent summit. (diagram)
Somatic cell nuclear transfer (SCNT) — Cloning by nuclear transfer: the egg's own spindle is removed, a somatic nucleus is injected and an electric or chemical pulse activates the reconstructed egg, whose cytoplasm reprogrammes the nucleus. (egg ≈ 100 µm)
Frog nuclear transfer (Gurdon, 1962) — The first proof that a specialised cell keeps all its genes: a nucleus from a tadpole gut cell, put into a UV-treated frog egg, gave a normal tadpole. (≈ 30 mm across)
Cell fusion with an ES cell — Fusing an ES cell with a somatic cell (with PEG or a virus) gives a heterokaryon with two nuclei, in which the somatic nucleus is reprogrammed, then a tetraploid hybrid. (≈ 25 µm)
Where iPSCs come from: skin, blood, urine — iPSCs can be made from a skin punch biopsy (fibroblasts), a blood sample (PBMCs, erythroblasts or T cells) or even urine (renal epithelial cells). (≈ 40 cm across)
Patient-specific disease modelling — From patient to dish: a patient's cells become iPSCs, which are turned into the affected cell type (here neurons with disease aggregates) and screened for drugs. (diagram)
Isogenic control lines (gene correction) — Correcting a patient's mutation with CRISPR–Cas9 gives an isogenic control line: the same genome except the one base, so any difference is due to the mutation. (diagram)
Reprogramming trajectory (single-cell map) — Single-cell RNA sequencing maps reprogramming as a path: fibroblasts move through early and intermediate states to a branch point where some become iPSCs and others stall or take other fates. (diagram)
Oct4–GFP reporter colonies — With a GFP reporter on the endogenous Oct4 gene, only fully reprogrammed colonies glow green under blue light; partially reprogrammed ones stay dim or patchy. (well ≈ 35 mm)
Protein reprogramming — The four factors made as proteins with a poly-arginine tag cross the cell membrane on their own and reach the nucleus — reprogramming without any genetic material (slow and inefficient). (scene ≈ 120 nm)
CRISPR activation of OCT4 and SOX2 — Catalytically dead Cas9 fused to activator domains is guided to the cell's own OCT4 and SOX2 promoters, opening the chromatin and switching the genes on without adding them. (≈ 70 nm)
The seesaw model of pluripotency — OCT4 pushes towards mesendoderm and SOX2 towards neuroectoderm; kept in balance, they hold the cell pluripotent — even lineage factors can replace them in reprogramming. (diagram)
Elite vs stochastic reprogramming — Two ideas for why only some cells reprogramme: only rare "elite" cells can, or every cell can but each needs a different, random amount of time. Evidence favours the stochastic model. (diagram)
Reprogramming blood cells — Blood cells (PBMCs or erythroblasts) are reprogrammed in suspension; a few settle onto the coated dish and grow into adherent iPSC colonies. (≈ 240 µm)
In vivo reprogramming mouse — A "reprogrammable" mouse carries a dox-inducible OSKM cassette in every cell. Doxycycline in the drinking water switches the factors on in the body; long induction makes teratomas, short cycles rejuvenate. (≈ 10 cm + tail)
Dolly the sheep (1996) — The first mammal cloned from an adult cell: a udder-cell nucleus from a white-faced Finn Dorset ewe went into an egg from a Scottish Blackface, carried by a Blackface surrogate. (diagram)

Epigenetic resetting 11

Promoter demethylation (bisulfite sequencing) — Bisulfite sequencing of the OCT4 or NANOG promoter: in fibroblasts most CpGs are methylated (black); in iPSCs almost all are unmethylated (white), as in ES cells. Each row is one sequenced clone. (diagram)
Bivalent chromatin — In pluripotent cells, developmental genes carry both an activating mark (H3K4me3, from MLL/COMPASS) and a repressive one (H3K27me3, from PRC2): silent but poised to switch on. (nucleosomes ≈ 11 nm)
Erasing and copying DNA methylation — TET enzymes oxidise 5-methylcytosine stepwise (5hmC, 5fC, 5caC) until repair restores plain cytosine; after replication, UHRF1 and DNMT1 copy methylation onto the new strand — block that and methylation is lost passively. (≈ 13 nm of DNA)
X-chromosome reactivation — Seen by RNA-FISH: female somatic and primed cells silence one X, coated by an XIST RNA cloud. Naive pluripotent cells have two active X chromosomes; primed human PSCs often lose XIST and partly reactivate it ("erosion"). (nucleus ≈ 15 µm)
Nuclear architecture: somatic vs pluripotent — Somatic nuclei have a thick lamina with lamin A/C, heterochromatin along the edge and many dense foci; pluripotent nuclei have a thin lamin-B lamina, open, hyperdynamic chromatin and large nucleoli. (nuclei ≈ 15 µm)
Telomere re-elongation — Reprogramming switches telomerase (TERT with its RNA, TERC) back on, so the short telomeres of an aged donor cell grow back to embryonic length in iPSCs. (chromosomes ≈ 7 µm)
Epigenetic clock reset — DNA methylation at certain CpGs changes predictably with age (the epigenetic clock). Reprogramming to iPSCs sets the clock back to about zero. (diagram)
3D genome rewiring — CTCF and cohesin fold chromatin into loops; in pluripotent cells OCT4, SOX2 and Mediator bring the OCT4 enhancer to its promoter, while in somatic cells the region is compacted against the lamina. (fibre ≈ 30 nm thick)
Epigenetic reprogramming in the zygote — Right after fertilisation the larger paternal pronucleus loses DNA methylation quickly (TET3 turns 5mC into 5hmC), while the maternal genome, protected by STELLA, keeps it longer. (zygote ≈ 100 µm)
Genomic imprinting (H19/IGF2) — Some genes are used from only one parent's copy. At H19/IGF2, CTCF on the unmethylated maternal control region blocks the enhancers from IGF2 (H19 on); the methylated paternal copy lets them reach IGF2. (diagram)
Methylation erasure in migrating germ cells — On their way from the hindgut to the genital ridges, primordial germ cells wipe almost all DNA methylation, including imprints, ready to be rewritten in eggs or sperm. (≈ 1 mm)

Pluripotency network & signalling 7

Core pluripotency network (OCT4–SOX2–NANOG) — OCT4, SOX2 and NANOG switch on their own genes and each other's, keep pluripotency genes on and hold developmental regulators off. The extended network adds KLF4, ESRRB, PRDM14, SALL4 and TFCP2L1. (diagram)
OCT4 and SOX2 on DNA — The SOX2 HMG box grips the minor groove and bends the DNA; OCT4's two-part POU domain binds next to it on the composite SoxOct motif that drives many pluripotency genes. (≈ 8 nm)
Super-enhancer condensate — Pluripotency genes are driven by clusters of enhancers bound by OCT4, SOX2, NANOG, Mediator and BRD4, which gather with RNA polymerase II into a phase-separated condensate at the promoter. (≈ 80 nm)
Signalling that keeps stem cells pluripotent — One signal at a time from the membrane to the genes: LIF–STAT3 (mouse naive), FGF2–ERK and Activin–SMAD2/3 (human primed), BMP4–SMAD1/5 and WNT–β-catenin. (diagram)
2i/LIF ground-state culture — Mouse ES cells stay in the naive ground state with LIF plus two inhibitors: a MEK inhibitor stops differentiation-driving ERK, and a GSK3 inhibitor stabilises β-catenin, which lifts TCF3 repression. (cell ≈ 14 µm)
NANOG heterogeneity (serum vs 2i) — In serum/LIF, mouse ES colonies are a mosaic of NANOG-high and NANOG-low cells that switch back and forth; in 2i/LIF, almost all cells are NANOG-high. (colony ≈ 80 µm)
LIN28 blocks let-7 — In pluripotent cells LIN28 binds the loop of pre-let-7 and recruits TUT4, which adds a U-tail that marks it for decay; in differentiated cells Dicer makes mature let-7, which silences LIN28, MYC and RAS. (≈ 20 nm)

Naive & primed states 2

Naive vs primed colonies — Naive pluripotent cells (like the pre-implantation epiblast) grow as compact domes; primed cells (like the post-implantation epiblast, and conventional human PSCs) grow as flat epithelial colonies. (≈ 200 µm)
The pluripotency continuum — Pluripotency changes as the epiblast develops: naive (E4.5, a ball of round cells), formative (E5.5, polarising into a rosette) and primed (E6.5, an epithelial cup), each with its own markers. (diagram)

Embryoid bodies & germ layers 6

Making embryoid bodies — Ways to aggregate pluripotent cells into embryoid bodies: hanging drops from an upturned lid, pyramidal microwells (one aggregate per well), U-bottom low-attachment wells, or free suspension in a low-attachment dish. (lid ≈ 90 mm)
Embryoid body development, cut open — An embryoid body grows from a solid aggregate wrapped in primitive endoderm, hollows out as its core dies, and becomes a fluid-filled cyst, sometimes with blood islands. Stain it to see the three germ layers. (≈ 0.1–0.5 mm)
Plated embryoid body outgrowth — An embryoid body plated on gelatin spreads into many cell types: neurons, beating cardiomyocytes, epithelial patches and fibroblast-like cells. (≈ 260 µm)
Three germ layers and what they become — Pluripotent cells make ectoderm (neurons, skin, melanocytes), mesoderm (heart muscle, blood, cartilage) and endoderm (liver, pancreatic β cells, lung). (diagram)
Trilineage differentiation test — A quick check of pluripotency: cells are directed into each germ layer and stained — PAX6 or NESTIN in neural rosettes, Brachyury in mesoderm, SOX17 or FOXA2 in endoderm. (fields ≈ 150 µm)
Micropatterned colony (2D gastruloid) — A round colony confined to a 500 µm micropattern and given BMP4 forms rings: ectoderm in the middle, then mesoderm and endoderm, and trophectoderm-like cells at the edge (Warmflash, 2014). (colony ≈ 500 µm)

Teratomas & chimaeras 11

Teratoma (excised) — The tumour PSCs form in a mouse: a lobulated mass with fluid-filled cysts, cartilage, pigment, hair and blood vessels — proof that the cells can make all three germ layers. (≈ 1–2 cm)
Teratoma section: three germ layers — An H&E section of a teratoma: neural rosettes and pigmented epithelium (ectoderm), cartilage and smooth muscle (mesoderm), and gut-like glands with goblet cells (endoderm). (block ≈ 0.4 mm)
Teratoma assay, step by step — The gold-standard test of human pluripotency: cells are injected (often with Matrigel) into an immunodeficient mouse, grow for 8–12 weeks, and the teratoma is removed and examined. (diagram)
Chimaeric mouse — A mouse grown from a blastocyst injected with ES cells: its coat mixes agouti patches from the ES cells (129 strain) with the host's black or white coat. (≈ 8 cm + tail)
Making chimaeras with ES cells — ES cells join a host embryo either by injection into the blastocyst cavity with a fine pipette or by pressing a zona-free 8-cell embryo against a clump of ES cells in a small well. (≈ 100 µm)
Tetraploid complementation — Fusing the two cells of a 2-cell embryo gives a tetraploid embryo that can only make placenta and yolk sac; with ES cells added, the whole fetus comes from the ES cells — the strictest test of pluripotency. (diagram)
Blastocyst complementation — A blastocyst that cannot make an organ (here Pdx1-deficient, no pancreas) is given PSCs from another animal; the donor cells fill the empty niche and build the whole organ. (diagram)
Teratoma injection sites — PSCs for a teratoma assay go under the skin, under the kidney capsule, into the testis or into a muscle of an immunodeficient mouse. (≈ 10 cm mouse)
Germline transmission — A chimaera is crossed with a black mouse: agouti pups come from ES-cell-derived sperm or eggs, proving the ES cells made the germline. (diagram)
Chimaeric embryo with labelled ES cells — An E10.5 mouse embryo grown from a blastocyst injected with GFP-labelled ES cells: green ES-derived cells are spread through every tissue. (≈ 5 mm)
Gene targeting in ES cells — Homologous recombination in mouse ES cells: a vector with two homology arms swaps a selection cassette into the gene (with HSV-tk outside the arms to select against random insertion) — the route to knockout mice. (diagram)

Gastruloids & germ cells 6

Mouse gastruloid — About 300 mouse ES cells aggregated and pulsed with a WNT activator break symmetry and elongate over five days, laying out a body axis: Brachyury at the posterior tip, a neural tube and somite-like segments. (≈ 0.1–0.5 mm)
Trunk-like structure — A gastruloid embedded in a little Matrigel builds a trunk: a neural tube flanked by pairs of segmented somites, with a tail bud and gut-like tube. (≈ 0.5 mm)
PGCLC induction aggregate — Germ cells made in a dish: epiblast-like cells aggregated with BMP4 give floating aggregates in which germ-cell-like cells (BLIMP1, AP2γ reporters) appear by day 4. (≈ 30–100 µm)
Reconstituted ovary (in vitro gametogenesis) — PGCLCs combined with fetal ovarian somatic cells form follicles with growing oocytes; matured eggs from them have given healthy mouse pups (Hayashi lab). (≈ 0.2–0.5 mm)
Segmentation clock in a human somitoid — Human PSC-derived presomitic mesoderm shows the segmentation clock: waves of HES7 sweep across the tissue every ~5 hours and somites bud off in rhythm. (≈ 0.6 mm)
Planarian neoblasts (adult pluripotent cells) — Planarian flatworms are full of neoblasts — dividing adult stem cells, some truly pluripotent: a single transplanted clonogenic neoblast can rebuild an entire worm. (≈ 1–2 cm)

Blood & bone marrow 23

Haematopoietic stem cell (surface markers) — A blood-forming stem cell: small and round with a large nucleus, studded with the surface markers used to sort it — human CD34⁺ CD90⁺ CD49f⁺ (CD38⁻ CD45RA⁻) or mouse c-Kit⁺ Sca-1⁺ CD150⁺ (CD48⁻). (≈ 6–8 µm across)
Dormant vs activated HSC (cut-away) — Two haematopoietic stem cells cut open. The dormant one is small and quiet — few mitochondria, lysosomes and compact chromatin, living on glycolysis; the activated one is larger, packed with mitochondria, endoplasmic reticulum and ribosomes as it leaves G0 to divide. (≈ 6 µm (dormant) and 10 µm (activated))
Endosteal HSC niche — The bone surface inside the marrow: a row of cuboidal osteoblasts and flat bone-lining cells, an osteoclast resorbing a pit that releases calcium, and haematopoietic stem cells sitting close to the endosteum with a sinusoid above. (≈ 150 µm across)
Perivascular HSC niche (sinusoid & CAR cells) — Most haematopoietic stem cells sit beside marrow sinusoids, touching the long processes of CXCL12-abundant reticular (CAR, LepR⁺) cells. These stromal cells and the sinusoid’s endothelium make the stem cell factor and CXCL12 the stem cells need. (≈ 100 µm across)
Arteriolar HSC niche with sympathetic nerve — Deep-quiescent haematopoietic stem cells near a small marrow arteriole wrapped by smooth-muscle cells and NG2⁺ pericytes. A sympathetic nerve fibre, sheathed by a non-myelinating Schwann cell, runs alongside and releases noradrenaline that tunes stem cell release over the day. (≈ 100 µm across)
Megakaryocyte HSC niche & proplatelets — A giant polyploid megakaryocyte beside a marrow sinusoid pushes beaded proplatelets through the wall to shed platelets into the blood. Stem cells resting against it are kept quiet by the CXCL4 and TGF-β1 it releases. (≈ 120 µm across)
Bone marrow block (trabeculae, sinusoids, fat) — A millimetre block of spongy bone: a lattice of trabeculae with haematopoietic marrow, sinusoids and fat cells in between. Red marrow is mostly blood-forming tissue; with age it turns into fatty yellow marrow. (≈ 1 mm block)
HSC mobilisation into a sinusoid — A sinusoid opened lengthwise: a haematopoietic stem cell squeezes through the endothelium into the blood while others already circulate. G-CSF lowers marrow CXCL12, and plerixafor blocks its receptor CXCR4, so stem cells let go of the niche — how donors’ stem cells are collected from blood. (≈ 60 µm across)
HSC homing: rolling, arrest & transmigration — Transplanted stem cells find the marrow in steps along the vessel floor: tethering and rolling on E- and P-selectin, arrest when CXCL12 switches on VLA-4 to grip VCAM-1, crawling, then squeezing between endothelial cells into the niche. (≈ 80 µm across)
Colony-forming unit (CFU) assay in methylcellulose — A gridded 35 mm dish of semi-solid methylcellulose two weeks after plating marrow or cord blood: each progenitor has grown into a colony — red, clustered BFU-E bursts, pale diffuse CFU-GM, compact macrophage CFU-M and large mixed CFU-GEMM — counted under the microscope. (35 mm dish)
Cobblestone areas on marrow stroma (LTC-IC assay) — Long-term marrow culture: primitive stem and progenitor cells creep under an adherent stromal layer and divide there as tight, phase-dark “cobblestone” patches, while their round offspring float above — a weeks-long test for the most primitive cells. (≈ 1 mm field)
Spleen colonies (CFU-S, Till & McCulloch) — The first proof of blood stem cells (Till and McCulloch, Toronto, 1961): marrow cells injected into irradiated mice formed raised nodules on the spleen, each a colony grown from one cell and able to make several blood lineages. (≈ 15 mm (mouse spleen))
Erythroblastic island — Red cells mature around a central “nurse” macrophage: from large blue proerythroblasts to small pink orthochromatic erythroblasts, which push out their nucleus (eaten by the macrophage) and leave as reticulocytes. (≈ 40 µm across)
HSC–niche contact: ligands & receptors — Close-up of the gap between a stem cell (top) and a niche stromal cell (bottom): membrane-bound stem cell factor binds KIT, CXCL12 binds CXCR4, angiopoietin-1 binds TIE2, thrombopoietin binds MPL and VCAM-1 grips the integrin VLA-4. Simplified shapes, not atomic structures. (≈ 0.2 µm gap (molecules ≈ 10–20 nm))
Clonal haematopoiesis in a marrow core — A marrow core cut lengthwise: one stem cell with a somatic mutation (often DNMT3A or TET2) has out-competed its neighbours, so a growing share of the marrow’s cells belong to its clone — common with age and a risk for blood cancer and heart disease. (≈ 2 mm core section)
Haemogenic endothelium in the dorsal aorta (AGM) — Where adult blood stem cells first arise: in the embryo’s dorsal aorta, Runx1⁺ endothelial cells on the ventral floor round up and bud into the lumen as intra-aortic clusters, the forerunners of every haematopoietic stem cell. (≈ 100 µm across)
Zebrafish CHT: endothelial “cuddling” of a stem cell — In the zebrafish larva’s tail, a newly arrived blood stem cell lodges in the venous plexus of the caudal haematopoietic tissue and nearby endothelial cells wrap around it in a pocket (“cuddling”), alongside a stromal cell that anchors it — seen directly by live imaging. (≈ 50 µm across)
Fetal liver: where blood stem cells expand — Before birth, blood stem cells settle in the fetal liver, where they multiply rapidly near portal vessels wrapped by Nestin⁺ NG2⁺ pericytes, among hepatoblasts and clusters of red-cell precursors, before moving on to the bone marrow. (≈ 150 µm across)
Extramedullary haematopoiesis in the spleen — Under stress — blood loss, infection, pregnancy or marrow disease — blood stem cells move to the spleen and start making blood there. They settle in the red pulp beside sinusoids and Tcf21⁺ stromal cells, away from the lymphocyte-filled white pulp. (≈ 0.5 mm across)
Blood progenitors seeding the thymus — The thymus has no self-renewing stem cells of its own: it is continually reseeded by progenitors from the bone marrow, which leave the blood through venules at the cortico-medullary junction (guided by P-selectin, CCR7 and CCR9) and then migrate out through the cortex as they become T cells. (≈ 300 µm across)
Paired-daughter assay in microwells — To ask whether a blood stem cell divides asymmetrically, single cells are placed in tiny wells, filmed as they divide, and the two daughters followed or separated for testing. Some daughter pairs inherit different amounts of lysosomes and mitochondria and take different fates. (wells ≈ 100 µm)
HSCs answering infection (emergency myelopoiesis) — Blood stem cells sense infection directly: interferons, IL-1 and microbial products bound by Toll-like receptors wake dormant HSCs, which divide and pour out myeloid cells (neutrophils and monocytes). Repeated bouts can exhaust them or leave a lasting “trained” memory. (≈ 60 µm)
Zebrafish kidney marrow — Fish have no bone marrow: in adult zebrafish blood is made in the kidney, where haematopoietic cells fill the spaces between the renal tubules, mostly in the head kidney. Whole kidney marrow is what researchers transplant to test zebrafish blood stem cells. (≈ 5 mm kidney)

Intestine & oesophagus 15

Intestinal crypt base: Lgr5 stem cells & Paneth cells — The bottom of a small-intestinal crypt cut open: slender Lgr5⁺ stem cells alternate with large Paneth cells full of red antimicrobial granules, which also feed the stem cells Wnt, EGF and Notch signals. Stromal trophocytes and telocytes wrap the base. (≈ 50 µm across)
Crypt cell positions: CBC, +4 and transit-amplifying zone — A whole crypt cut lengthwise, coloured by position counted from the base: Lgr5⁺ columnar stem cells between Paneth cells at positions 0–3, the debated “+4” reserve cells just above, then rapidly dividing transit-amplifying cells that move up and out. (≈ 50 × 120 µm)
Crypt fission — A crypt splitting in two from the bottom up, as the gut grows or after injury: a wedge of Paneth cells forms at the base and the stem cell zone divides into two daughter crypts sharing one opening — how clones spread along the intestine. (≈ 80 µm across)
Wnt and BMP gradients along the crypt–villus axis — The gut’s stem cell niche is set by opposing gradients from the stroma beneath the epithelium: Wnt and R-spondin (with the BMP blocker Gremlin from trophocytes) are strongest around the crypt base, while telocytes at the villus base pump out BMP, which drives cells to mature as they climb. (≈ 0.5 mm tall)
Lgr5 lineage tracing: a labelled ribbon — Days after one Lgr5⁺ stem cell is genetically labelled, its descendants form a continuous ribbon from the crypt base up one side of the villus to the tip — proof that crypt base cells are the stem cells. The epithelium is replaced every four to five days. (≈ 0.4 mm tall)
Neutral drift to a monoclonal crypt — The ring of about 14–16 stem cells at a crypt base, seen at five time points: neighbours randomly replace one another, so a labelled clone drifts until it either takes over the whole crypt (monoclonal) or is lost — no stem cell is special. (5 crypt bases, each ≈ 50 µm)
Crypt injury and revival stem cells — After radiation the crypt’s Lgr5⁺ stem cells die (dark apoptotic bodies). Rare clusterin-positive “revival” cells and dedifferentiating progenitors switch to a fetal-like, YAP-driven state and rebuild an enlarged regenerating crypt that restores the stem cell pool. (≈ 60 µm across)
Colonic crypt stem cells (Reg4 niche) — A long, straight colonic crypt cut in half. The colon has no Paneth cells: Lgr5⁺ stem cells at the base are interspersed with Reg4⁺ deep crypt secretory cells that play the niche role, and goblet cells full of mucin line most of the crypt. (≈ 50 × 300 µm)
Oesophageal basal progenitor layer — A thin slice through the oesophagus: its lining is a stratified squamous epithelium renewed by a single layer of equipotent basal progenitors (p63⁺, Sox2⁺), whose daughters flatten as they move up to the folded lumen and are shed. (≈ 2 mm across (mouse))
Paneth cell feeding an Lgr5 stem cell (niche signals) — Close-up of a large Paneth cell (granules at its tip) beside a slender Lgr5⁺ stem cell. Membrane-bound Wnt3, EGF and Delta-like ligands pass by direct contact; R-spondin from the stroma below binds Lgr5 and keeps the stem cell’s Wnt receptors on its surface. (≈ 25 µm tall)
Cell shedding at the villus tip — The end of the conveyor: enterocytes made in the crypt reach the villus tip after a few days and are squeezed out by an actomyosin ring in their neighbours, which close the gap so the barrier never leaks. (≈ 80 µm across)
Gastric corpus gland: isthmus stem cells and chief cell reserve — A gland of the stomach body cut in half: fast-cycling stem cells in the narrow isthmus make pit cells upwards and parietal, neck and chief cells downwards. Mature chief cells at the base (Troy⁺) act as a reserve, reverting to dividing progenitors after injury. (≈ 0.5 mm deep)
Paligenosis: a mature cell returning to the cell cycle — A mature secretory cell can turn back into a dividing progenitor in a set programme called paligenosis: first it digests its own secretory machinery (autophagy and lysosomes), then it switches on progenitor genes, and finally mTORC1 restarts and it enters the cell cycle. (≈ 20 µm cells)
Intestinal mucosa: a field of villi and crypts — A block of small-intestine lining: finger-like villi stand above the surface while several crypts, each with its own ring of stem cells at the bottom (green), dip down around the base of every villus — about six to ten crypts feed each villus. (≈ 1 mm block)
Enteric nervous system progenitors in the gut wall — A slice of the gut wall: ganglia of the myenteric plexus between the two muscle coats, and the smaller submucosal plexus. Neural-crest-derived enteric glia and progenitors (Sox10⁺) in these ganglia can make new neurons in culture and after injury — the target of stem cell therapies for Hirschsprung disease. (≈ 1 mm across)

Skin, hair & nail 17

Hair follicle stem cell compartments — A growing (anagen) hair follicle cut lengthwise, coloured by compartment: bulge stem cells (K15⁺, CD34⁺) where the arrector pili muscle attaches, the isthmus and infundibulum above, and the matrix wrapped around the dermal papilla at the base that builds the hair shaft. (≈ 2–3 mm long (human scalp))
Hair cycle: anagen, catagen, telogen — Three follicles in the three phases of the hair cycle. In growth (anagen) the bulb sits deep with its dermal papilla; in regression (catagen) the lower follicle shrinks to a strand that drags the papilla upwards; at rest (telogen) a club hair sits in the bulge with a small hair germ above the papilla, ready to start the next cycle. (≈ 2 mm tall)
Resting bulge and hair germ (cell level) — A resting follicle at cell level, cut open: the club hair is held by an inner layer of K6⁺ niche cells, wrapped by the outer bulge stem cells; the small hair germ beneath touches the dermal papilla. BMP keeps them quiet — when the papilla’s Wnt and FGF signals win, the hair germ starts the next growth phase. (≈ 150 µm tall)
Epidermal proliferative unit — Interfollicular epidermis organised as a column: a basal patch with a slow-cycling stem cell surrounded by dividing progenitors, and above it a neat stack of flattening cells — spinous, granular and finally hexagonal cornified squames that are shed from the surface. (≈ 30 µm wide, 50 µm tall (mouse))
Basal cell division: parallel vs perpendicular — Epidermal stem cells choose how to divide. With the spindle parallel to the basement membrane both daughters stay basal (symmetric, self-renewing); with LGN–NuMA recruited to the top of the cell the spindle turns perpendicular and one daughter is pushed up to differentiate (asymmetric, stratifying). (≈ 40 µm across)
Sebaceous gland renewal (holocrine) — A sebaceous lobule cut open: small progenitor cells (Lrig1⁺, Blimp1⁺) at the rim divide and push their daughters inwards, where they swell with lipid droplets and finally burst to release sebum into the hair canal — the whole gland is renewed this way every week or two. (≈ 200 µm across)
Sweat gland and its progenitors — An eccrine sweat gland: a tightly coiled secretory tube deep in the dermis and a duct spiralling up through the epidermis. Its myoepithelial (basal) and luminal cells are separate, largely self-renewing lineages; the duct cells also help repair the skin surface after wounding. (≈ 0.4 mm coil)
Melanocyte stem cells and hair greying — The lower part of a growing follicle: unpigmented melanocyte stem cells wait in the bulge and hair germ; their offspring move down to the bulb, become dendritic pigment cells and hand melanin to the cells that build the hair. When the stem cells are lost or get stuck, new hairs grow in grey. (≈ 1 mm (lower follicle))
Wound re-epithelialisation from stem cells — A skin wound a few days on: epithelial tongues crawl in from the edges beneath the scab, fed by interfollicular stem cells and by bulge and isthmus cells streaming up from nearby hair follicles, while granulation tissue fills the gap below. (≈ 2 mm across)
Wound-induced hair neogenesis — In large mouse wounds the healed centre does something adult skin normally cannot: it grows brand-new hair follicles. Epidermal cells form placodes over Wnt-active dermal condensates and bud downwards as if in the embryo, while the scar edges stay hairless. (≈ 1 cm wound)
Nail unit and its matrix stem cells — A fingertip cut lengthwise: the nail plate is made by the matrix tucked under the proximal nail fold, where Lgr6⁺ stem cells at its base keep it growing about 3 mm a month; the pale lunula is the visible tip of the matrix. Nail stem cells also help the fingertip regenerate. (≈ 2 cm (human fingertip))
Keratinocyte holoclone, meroclone and paraclone — Single skin keratinocytes grown on feeder cells make three kinds of colony: big, round, smooth-edged holoclones of small cells (stem cells), wrinkled meroclones, and small, irregular paraclones of large flat cells that soon stop dividing. Stained red, as in clonal analysis. (3 wells of a 6-well plate)
Hair follicle cross-section at the bulge — A follicle cut across at the level of the bulge, showing its concentric layers: the hair shaft (medulla, cortex, cuticle) inside the inner root sheath and companion layer, then the outer root sheath whose basal layer — on the basement membrane — holds the bulge stem cells, all wrapped in a connective-tissue sheath. (≈ 150 µm across)
Epidermal clones seen from above (lineage tracing) — Mouse epidermis seen from above weeks after multicolour clonal labelling: patches of every size, from single cells to large clones, reflect stem cells and committed progenitors dividing and their offspring being lost at random — the size distribution reveals the rules of skin renewal. (≈ 1 mm field)
Follicle miniaturisation in pattern balding — In pattern balding, big terminal follicles shrink step by step into tiny ones making fine, almost invisible vellus hairs. Biopsies show the bulge stem cells are still there — what is lost are the CD34⁺ progenitors they should activate — which is why hair regrowth may be possible. (≈ 3 mm tall)
Tail epidermis: scale and interscale lineages — Mouse tail skin, a favourite for whole-mount studies, is a mosaic: rows of scales (shed without nuclei clearing fully — parakeratotic) alternate with interscale (normal) epidermis around groups of three hair follicles. Each region is kept by its own pool of stem cells. (≈ 1 mm field)
Hair patch assay: making follicles from cells — A test of hair-forming stem cells: dissociated epidermal cells mixed with inductive dermal papilla cells and injected under the skin of a nude mouse self-organise within two weeks into a cyst bristling with new, complete hair follicles. (≈ 3 mm cyst)

Skeletal muscle 9

Satellite cell niche (fibre cross-section) — A muscle fibre cut across: the satellite cell (Pax7⁺) is a flat, quiescent stem cell squeezed between the fibre’s membrane and its basal lamina, usually close to a capillary, among the fibre’s own peripheral myonuclei. (≈ 60 µm fibre)
Satellite cell activation along a fibre — Steps a satellite cell takes after injury, laid out along one fibre: thin and quiescent under the basal lamina, then swollen and alert, dividing, and finally releasing MyoD⁺ myoblasts that multiply before fusing to repair the fibre. (≈ 150 µm of fibre)
Asymmetric satellite cell division — A satellite cell dividing at right angles to the fibre leaves one daughter on the basal lamina that stays a Pax7⁺ Myf5⁻ stem cell, while the daughter touching the fibre switches on Myf5 and commits to muscle; dividing along the fibre gives two equal stem cells. (≈ 40 µm patch)
Isolated myofibre culture with satellite cell clusters — A single fibre teased from a mouse muscle and floated in medium: after three days each satellite cell has made a little cluster on the fibre, where some cells keep Pax7 and return to quiescence while others switch on MyoD and myogenin to differentiate. (≈ 4 mm fibre in a well)
Muscle regeneration after injury (cross-section) — A bundle of fibres cut across, through an injury. Damaged fibres die and are cleared by macrophages; satellite cell–derived myoblasts multiply and fuse inside the old basal lamina tubes, making small new fibres recognisable by their central nuclei, which grow back to full size. (≈ 0.4 mm across)
Fibro-adipogenic progenitors between fibres — Muscle fibres side by side with the interstitium between them: stellate PDGFRα⁺ fibro-adipogenic progenitors help satellite cells repair the muscle — but in chronic disease or old age they turn into fat cells and scar-forming fibroblasts. (≈ 200 µm across)
Satellite cell adhesion and signalling contacts — The satellite cell’s two faces: underneath, M-cadherin joins it to the fibre, which also offers Notch ligands; on top, integrin α7β1 grips laminin in the basal lamina. Notch signalling and collagen V keep it quiescent; Wnt7a from regenerating fibres makes it divide symmetrically. (≈ 20 µm)
Satellite cells in young and old muscle — Two fibres compared: young (left) with several satellite cells resting quietly under the basal lamina, and old (right) with fewer, some senescent (p16⁺) and some woken prematurely by FGF2 from the aged fibre, while the lamina thickens — part of why old muscle repairs poorly. (≈ 100 µm of fibre each)
Satellite cells in Duchenne muscular dystrophy — In Duchenne dystrophy the fibres lack dystrophin and tear easily; satellite cells also express dystrophin, and without it they lose their polarity and divide asymmetrically far less often, so they make too few committed progenitors to keep up (Dumont and Rudnicki, Ottawa, 2015). (≈ 100 µm of fibre)

Brain & spinal cord 19

Subventricular zone niche (pinwheels) — The wall of the lateral ventricle seen from inside and below: multiciliated ependymal cells form pinwheels around the tiny apical tips of B1 stem cells, each with one primary cilium touching the cerebrospinal fluid. Underneath, the B1 cells reach down to blood vessels, near clusters of dividing C cells and chains of A-cell neuroblasts. (≈ 80 µm across)
B1 neural stem cell (apical and basal contacts) — One B1 stem cell spans its niche like an embryonic radial glial cell: a thin apical process ends at the ventricle with a single primary cilium bathed in cerebrospinal fluid, and a long basal process ends in a foot on a blood vessel, reading signals from both. (≈ 50 µm long)
Rostral migratory stream (neuroblast chains) — Newborn neurons from the subventricular zone travel several millimetres to the olfactory bulb by sliding along one another in chains, inside a sleeve of astrocyte processes (the glial tube) and guided by blood vessels running alongside. (≈ 100 µm of the stream)
New neurons integrating in the olfactory bulb — A slice of the olfactory bulb: neuroblasts arriving from the rostral migratory stream leave the bulb’s core and migrate outwards, becoming granule cells deep in the bulb or periglomerular cells around the glomeruli where smell inputs arrive. (≈ 1.5 mm across (mouse))
Subgranular zone niche (dentate gyrus) — The hippocampal stem cell niche: radial glia-like stem cells sit at the border between the hilus and the granule cell layer, sending one branched process up through the layer. Their progeny — intermediate progenitors, neuroblasts and immature neurons — lie along this subgranular zone beside capillaries. (≈ 100 µm across)
Hippocampal slice with the neurogenic zone — A slice through the hippocampus: the C-shaped pyramidal layer of CA1–CA3 and the V-shaped granule cell layer of the dentate gyrus, whose inner edge — the subgranular zone, highlighted — keeps making new granule neurons through adult life in rodents (and, as debated, humans). (≈ 3 mm slice (mouse))
Adult hippocampal neurogenesis, stage by stage — The path from stem cell to neuron in the dentate gyrus, left to right: a radial glia-like type-1 cell, dividing type-2 progenitors, a DCX⁺ type-3 neuroblast, an immature neuron sprouting its dendrite, and after about four weeks a mature granule neuron with a spiny dendritic tree and a mossy-fibre axon. (cells ≈ 10 µm; mature dendrites ≈ 200 µm)
Radial glia scaffold of the developing cortex — A wedge of embryonic cortex: radial glia — the brain’s founding neural stem cells — stretch from the ventricle (bottom) to the pial surface (top). They divide at the ventricle, make intermediate progenitors, and their long fibres are the rails newborn neurons climb to the cortical plate. (≈ 200 µm tall (mouse embryo))
Interkinetic nuclear migration — In the pseudostratified neuroepithelium every cell spans the full height, but its nucleus moves with the cell cycle: up towards the basal side in G1, DNA synthesis (S) at the top, back down in G2, and mitosis right at the apical (ventricular) surface, where the cells round up. (≈ 60 µm tall)
Outer radial glia in the human OSVZ — The human cortex grows so large partly thanks to outer radial glia: stem cells in a thick outer subventricular zone that keep only a basal fibre to the pial surface. They divide after a jump of the cell body (mitotic somal translocation), and their fibres fan out to support a much wider cortical plate. (≈ 1 mm tall (human, mid-gestation))
Tanycytes lining the third ventricle — A slice through the base of the hypothalamus: specialised radial cells called tanycytes line the third ventricle, sending long processes into the arcuate nucleus and down to the capillary loops of the median eminence. Some act as adult neural stem cells that can make new appetite-regulating neurons. (≈ 0.5 mm across)
Spinal cord ependymal cells and injury response — A slice of spinal cord: the central canal is lined by ependymal cells that sit quietly in health. After an injury they wake up, divide and stream towards the lesion, where their offspring become a big share of the scar-forming astrocytes. (≈ 1 mm across (mouse))
Oligodendrocyte precursor cells tiling the brain — Adult oligodendrocyte precursors (NG2 glia) are the brain’s most numerous dividing cells. Each patrols its own territory with bushy processes and repels its neighbours; when one divides or matures into a myelinating oligodendrocyte, another quickly fills the gap. (≈ 200 µm across)
Neurogenic niches of the adult mouse brain — Where new neurons are born in the adult mouse brain: along the walls of the lateral ventricles (subventricular zone), from where they stream forward to the olfactory bulb, in the dentate gyrus of the hippocampus, and — at a lower rate — around the third ventricle in the hypothalamus. (≈ 1.5 cm (mouse brain))
Human subventricular zone: the astrocyte ribbon — The human ventricle wall is layered differently from the mouse’s: ependymal cells, then a nearly cell-free gap of processes, then a ribbon of astrocytes that includes neural stem cells. Neurogenesis here is lively in infancy (feeding the frontal cortex) and almost stops in adults. (≈ 200 µm deep)
Zebrafish pallium radial glia (regeneration) — In the adult zebrafish forebrain, which folds outward (everted), radial glial stem cells line the outer ventricular surface with long processes reaching deep. Fish keep many active neurogenic zones throughout life and regenerate neurons after injury, unlike mammals. (≈ 0.5 mm across)
Choroid plexus feeding the SVZ niche — Frond-like folds of choroid plexus float in the ventricle and secrete cerebrospinal fluid rich in growth factors (such as IGF2 and BMP5). Carried by the flow, these reach the primary cilia of B1 stem cells poking through the ventricle wall and tune their activity — a long-range niche signal that weakens with age. (≈ 1 mm across)
SVZ vascular plexus and dividing cells — A whole mount of the ventricle wall seen from below: a flat, specialised network of blood vessels runs under the subventricular zone. Dividing stem cells and transit-amplifying cells cluster on these vessels, often where the blood–brain barrier is leaky, picking up signals from blood and endothelium. (≈ 300 µm field)
Striatal astrocytes making neurons after stroke — Ordinary astrocytes can harbour a dormant neuron-making programme. After a stroke, reduced Notch signalling lets some striatal astrocytes (normally star-shaped support cells) divide and turn into neuroblasts and new neurons near the damaged area. (≈ 300 µm across)

Mesenchymal & skeletal 13

Mesenchymal stromal cells in culture (swirls) — Mesenchymal stromal cells growing on plastic: large, flat, spindle-shaped cells that line up in parallel streams and swirls as they approach confluence, with the odd rounded cell dividing — the first of the ISCT criteria is simply sticking to plastic. (≈ 1 mm field)
MSC trilineage differentiation (bone, fat, cartilage) — The classic test of a mesenchymal stromal cell: in osteogenic medium it lays down mineral nodules (Alizarin Red), in adipogenic medium it fills with lipid droplets (Oil Red O), and packed into a pellet with TGF-β it makes cartilage matrix (Alcian blue). (2 wells and a pellet tube)
Mesenchymal stromal cell (ISCT surface markers) — A single mesenchymal stromal cell spread on a surface: a flat spindle with leading lamellipodia, a large oval nucleus and the three surface markers that define it — CD73, CD90 and CD105 — while lacking blood-cell markers such as CD34, CD45 and HLA-DR. (≈ 50–80 µm long)
CFU-F colonies (crystal violet) — Friedenstein’s colony test: bone marrow cells plated at low density leave scattered fibroblast-like colonies after two weeks, each grown from one stromal progenitor. Stained purple with crystal violet, they are counted to measure how many such progenitors a sample holds. (60 mm dish)
Growth plate resting-zone stem cells — A slice through a growth plate: round PTHrP⁺ stem cells in the resting zone, kept by a niche formed under the secondary ossification centre, feed clonal columns of flattened proliferating chondrocytes that swell (hypertrophic zone) and are replaced by bone below. One column is shown as a labelled clone. (≈ 0.5 mm tall)
Periosteal stem cells and fracture callus — A long bone with a healing fracture, cut lengthwise: the periosteum’s inner cambium layer holds skeletal stem cells that swell into a callus around the break — cartilage (blue) bridging the gap, turning into woven bone at its edges, while marrow fills the shaft. (≈ 1 cm (mouse tibia))
Adipose tissue and its perivascular progenitors — A lobule of white fat: huge lipid-filled adipocytes packed together, threaded by capillaries. The cells that make new adipocytes — and the adipose-derived stromal cells used in the clinic — sit along these vessels as small perivascular progenitors. (≈ 0.5 mm across)
Pericytes as perivascular progenitors — A capillary with its pericytes: bump-on-a-log cell bodies whose long processes wrap the vessel under a shared basement membrane. Pericytes (NG2⁺, PDGFRβ⁺, CD146⁺) from many organs behave like mesenchymal stromal cells in culture and are thought to be one of their natural sources. (≈ 60 µm of capillary)
MSC immunomodulation and secreted vesicles — Much of what mesenchymal stromal cells do as a therapy is by secretion rather than becoming new tissue: they release extracellular vesicles and factors such as PGE2, IDO and TSG-6 that calm T cells and turn macrophages towards a repair-promoting (M2) state. (≈ 80 µm across)
Tendon stem/progenitor cells — A tendon cut across and lengthwise: bundles of aligned collagen fibres (fascicles) with rows of elongated tenocytes between the fibres. A small population of tendon stem/progenitor cells lives in the tendon and its sheath (epitenon), and responds to injury. (≈ 0.5 mm across)
Articular cartilage superficial-zone progenitors — A block of joint cartilage: flat cells at the surface — lubricin-making Prg4⁺ progenitors — slowly give rise to the rounder chondrocytes of the middle zone and the stacked cells of the deep zone, above the tidemark, calcified cartilage and subchondral bone. (≈ 0.5 mm deep)
Umbilical cord and Wharton’s jelly stromal cells — An umbilical cord cut across: two arteries and one vein embedded in Wharton’s jelly, a gel-like connective tissue under the amniotic covering. Stromal cells in the jelly (and around the vessels) are a popular source of mesenchymal stromal cells, alongside the blood stem cells in cord blood. (≈ 1.5 cm across)
Cranial suture stem cells — Between two growing skull bones runs a narrow seam of suture mesenchyme. Gli1⁺ (and Axin2⁺) stem cells in its middle feed the advancing bone fronts on either side; if they are lost, the bones fuse early (craniosynostosis) and the skull cannot grow. (≈ 0.5 mm across)

Eye 6

Limbal stem cell niche (palisades of Vogt) — The front of the eye with the cornea’s rim highlighted: the limbus, where radial ridges called the palisades of Vogt and the crypts between them shelter the stem cells that renew the corneal epithelium, their daughters drifting in towards the centre of the cornea. (≈ 12 mm cornea (human))
Limbal epithelial crypt (cell level) — A slice through the limbus: small, tightly packed basal stem cells (p63α⁺, ABCG2⁺) line a crypt dipping into the stroma, shielded by pigment from melanocytes and supported by stromal niche cells and nearby vessels; to one side the clear cornea, to the other the conjunctiva. (≈ 300 µm across)
Corneal clone stripes (centripetal renewal) — Seen from the front weeks after multicolour labelling, the corneal epithelium is covered in coloured stripes that run from the limbus to the centre like spokes: each is a clone made by one limbal stem cell, pushed inwards as cells are lost from the surface (the X, Y, Z hypothesis). (≈ 3 mm (mouse cornea))
Ciliary marginal zone of the fish retina — Fish and frogs keep growing their eyes all their lives from a ring of retinal stem cells at the very edge of the retina, the ciliary marginal zone. Cells mature as they are left behind, so the retina is laid down in rings like a tree, oldest at the centre. (≈ 1 mm eye (zebrafish))
Müller glia regenerating the retina — A slice of retina with its Müller glia spanning every layer. In zebrafish, injury makes a Müller cell re-enter the cell cycle: its nucleus migrates to divide at the outer edge and it gives rise to a cluster of progenitors that replace lost neurons — something mammalian Müller glia barely do. (≈ 200 µm thick)
Lens epithelium and its germinative zone — The lens grows all life long. A single layer of epithelium covers its front; just in front of the equator (the germinative zone) cells divide, move round the equator and stretch into long, transparent fibre cells that are laid down in layers like an onion. Infant lenses can regrow from these cells after cataract surgery. (≈ 10 mm (human lens))

Breast, prostate & glands 7

Mammary duct bilayer and its stem cells — A breast duct cut lengthwise: an inner layer of luminal cells around the lumen and an outer layer of contractile basal (myoepithelial) cells on the basement membrane. Stem cell activity is found in the basal layer; in the adult most lineages are maintained by unipotent progenitors. (≈ 80 µm across)
Terminal end bud (puberty) — At puberty the mammary ducts grow into the fat pad behind club-shaped terminal end buds: a single outer layer of cap cells (rich in stem cell activity) around a solid mass of body cells, which hollow out by apoptosis to form the lumen behind the advancing tip. (≈ 0.3 mm long)
Mammary alveoli from luminal progenitors — In pregnancy, luminal progenitors along the terminal ducts multiply into grape-like clusters of alveoli, each a ball of milk-making cells wrapped in a basket of myoepithelial cells; after weaning most are removed again (involution). (≈ 0.5 mm lobule)
Whole mammary tree from one transplanted cell — The classic proof of mammary stem cells (Shackleton and Stingl, 2006): a single basal cell placed into a mouse fat pad cleared of its own epithelium regrows a complete, branching ductal tree that fills the pad and can make milk. (≈ 1.5 cm fat pad (mouse))
Prostate gland basal and luminal progenitors — A prostate gland cut in half: infolded tubes with tall luminal (androgen-dependent secretory) cells on a basal layer of p63⁺ cells, plus scattered neuroendocrine cells. After castration the gland shrinks; rare castration-resistant luminal cells (CARNs) and basal cells regrow it when androgen returns. (≈ 200 µm acinus)
Salivary gland acini and duct progenitors — A salivary gland lobule: berry-like acini of secretory cells, hugged by myoepithelial cells, drain through thin intercalated ducts (home to Kit⁺ and Ascl3⁺ progenitors) into striated ducts. Acinar cells also renew themselves (Sox2⁺) — relevant to restoring saliva after radiotherapy. (≈ 0.3 mm lobule)
Endometrial regeneration from the basalis — The lining of the uterus rebuilds itself every month. Its shed upper layer (functionalis) regrows from the permanent basalis, where the bases of the glands hold SOX9⁺/SSEA-1⁺ epithelial progenitors and SUSD2⁺ perivascular stromal stem cells wrap the spiral arterioles. (≈ 5 mm thick (proliferative phase))

Germline stem cells 8

Spermatogonial stem cell niche (seminiferous tubule) — A wedge of a seminiferous tubule: undifferentiated spermatogonia rest on the basement membrane, gathering where the tubule faces blood vessels and interstitial Leydig cells. Sertoli cells, spanning to the lumen, and the outer myoid cells release GDNF that keeps them self-renewing, while their descendants move inwards as spermatocytes and spermatids. (≈ 200 µm tubule)
Spermatogonial chains: As, Apr and Aal — Undifferentiated spermatogonia seen on the tubule surface: single cells (As), pairs (Apr) and chains of 4, 8 and 16 (Aal) still joined by intercellular bridges after division. Chains can break apart again, so cells that look committed may return to being stem cells. (≈ 150 µm of tubule surface)
Spermatogonial stem cell transplantation — Brinster’s test for germline stem cells (1994): donor testis cells injected into the tubules of a mouse whose own germ cells were removed grow into blue-stained segments of complete spermatogenesis — each colony started by one stem cell — and can restore fertility. (≈ 6 mm (mouse testis))
Drosophila testis hub and stem cells — The tip of a fruit-fly testis, a classic stem cell niche: a tight knot of hub cells is ringed by about nine germline stem cells, each flanked by two thin cyst stem cells. The hub’s Upd signal keeps them stem; each germline stem cell divides with its spindle pointing away from the hub, pushing a gonialblast out to form a cyst. (≈ 40 µm tip)
Drosophila germarium (ovarian stem cell niche) — The front of a fly ovariole: stacked terminal-filament cells and cap cells make the niche, where two or three germline stem cells hold on and receive Dpp (BMP). Daughters pushed away become cystoblasts, divide four times into 16-cell cysts linked by a branched fusome, and bud off as egg chambers wrapped in follicle cells. (≈ 100 µm long)
C. elegans gonad and the distal tip cell — One arm of a worm’s gonad: a single distal tip cell caps the end and wraps the germ cells in long processes, giving LAG-2 (Delta) to their GLP-1 (Notch). Within reach they keep dividing as stem cells; further along they enter meiosis (crescent nuclei, then pachytene), turn round the loop and grow into oocytes. (≈ 250 µm arm)
Ovarian surface epithelium repairing after ovulation — Every ovulation tears the ovary’s surface. The single-layered surface epithelium heals the wound each cycle, renewed by Lgr5⁺ progenitor cells — some concentrated at the hilum — while a corpus luteum forms in the emptied follicle below. (≈ 3 mm (mouse ovary))
Germline stem cell clumps in culture — Spermatogonial stem cells can be grown for years with GDNF and FGF2 on feeder cells, where they form characteristic grape-like clumps of tightly linked round cells. Transplanted back into a testis, they still make sperm and healthy offspring. (≈ 1 mm field)

Liver & pancreas 6

Liver lobule zonation and pericentral Axin2 cells — A hexagonal liver lobule: plates of hepatocytes run from the portal triads at the corners to the central vein. Endothelial cells of the central vein secrete Wnt, so the hepatocytes around it (Axin2⁺) form a self-renewing ring that slowly replaces cells outwards; zones 1–3 differ in metabolism. (≈ 1 mm across)
Canal of Hering and the ductular reaction — Where hepatocytes’ bile canaliculi join the bile ducts of a portal triad — the canal of Hering — lie bipotent progenitor cells. In chronic injury they multiply into branching ductules that push into the liver tissue (the ductular reaction) and can make new hepatocytes and cholangiocytes. (≈ 150 µm across)
Liver regrowth after partial hepatectomy — Remove two-thirds of a mouse liver (the median and left lateral lobes) and the remaining lobes grow until the original mass is restored, in about a week — mostly by existing hepatocytes dividing rather than by stem cells. (≈ 2 cm (mouse liver))
Pancreatic acinus with centroacinar cells — A pancreatic acinus cut open: pyramidal acinar cells with zymogen granules at their tips, and pale centroacinar cells — the start of the duct — sitting inside the lumen. Centroacinar and terminal duct cells (Aldh1⁺) show progenitor-like behaviour; whether adult ducts make new beta cells is still debated. (≈ 40 µm acinus)
Peribiliary glands of the bile ducts — A large bile duct cut across: tiny peribiliary glands nest in its wall and connect to the lumen. They hold multipotent biliary-tree stem cells that can renew the duct lining after injury and in culture can make liver or pancreatic cells. (≈ 1 mm across)
New beta cells: replication rather than stem cells — An islet next to a small duct: in adults, new insulin-making beta cells come mainly from existing beta cells dividing (a few shown in mitosis), not from a dedicated stem cell — as Dor and Melton’s lineage tracing showed in 2004. Duct-derived neogenesis remains debated. (≈ 150 µm islet)

Lung & airway 8

Airway epithelium and its basal stem cells — The lining of the windpipe and bronchi: a pseudostratified layer in which every cell touches the basement membrane. Small triangular basal cells (Krt5⁺, p63⁺) are its stem cells, making club, goblet and multiciliated cells; rarer neuroendocrine cells and ionocytes are scattered among them. (≈ 60 µm across)
Alveolar type 2 stem cells and their niche — Alveoli cut open: thin, sprawling type 1 cells make the gas-exchange surface, while cuboidal type 2 cells in the corners make surfactant (lamellar bodies) and are the alveoli’s stem cells. Wnt-making fibroblasts sit right next to the type 2 cells that will divide. (≈ 200 µm across)
Type 2 to type 1 transition (repair) — How a damaged alveolus is resurfaced, left to right: a cuboidal type 2 stem cell, a transitional Krt8⁺ cell that stretches and flattens (a stage that can stall in lung fibrosis), and finally a huge, thin type 1 cell covering the capillaries. (≈ 100 µm across)
Bronchioalveolar stem cells at the duct junction — Where the smallest airway, the terminal bronchiole, opens into the alveoli: club cells line the bronchiole, and right at the junction sit rare bronchioalveolar stem cells that carry markers of both club cells (Scgb1a1) and type 2 cells (Sftpc) and can repair either side. (≈ 200 µm across)
Neuroepithelial body and variant club cells — A cluster of neuroendocrine cells (a neuroepithelial body) in a bronchiole, touched by nerve fibres. The club cells around it lack the enzyme that activates the toxin naphthalene, so they survive and regrow the lining — and the neuroendocrine cells themselves can act as reserve stem cells. (≈ 80 µm across)
Krt5⁺ pods after severe lung injury — After severe damage such as influenza, the alveoli are not always rebuilt properly: airway-derived Krt5⁺ cells swarm into the injured region and form solid, keratin-rich pods that patch the lung like scar tissue instead of new gas-exchange surface. (≈ 1 mm across)
Airway submucosal gland and myoepithelial stem cells — Beneath the windpipe’s lining, submucosal glands pour mucus and fluid through a duct to the surface. Their basket-like myoepithelial cells are reserve stem cells: after severe injury they can climb out and rebuild the surface epithelium. (≈ 0.5 mm deep)
Trachea with its basal stem cell layer — A segment of windpipe cut open: C-shaped cartilage rings and the trachealis muscle behind, a lining of pseudostratified epithelium whose bottom layer of basal stem cells (green) renews it, and submucosal glands opening between the rings. (≈ 2 cm segment (human))

Teeth 5

Dental pulp stem cells and reparative dentine — A molar cut in half: under the enamel and dentine is the soft pulp, lined by odontoblasts. Pulp stem cells (DPSCs) sit around its blood vessels; when a deep cavity kills odontoblasts, they make new odontoblast-like cells that wall off the pulp with a bridge of reparative dentine. (≈ 1 cm (human molar))
Mouse incisor cervical loop (ever-growing tooth) — Rodent incisors never stop growing. At their root end the labial cervical loop — a bulb of epithelium with a loose stellate reticulum core holding Sox2⁺ stem cells — feeds a transit-amplifying zone and then the ameloblasts that lay enamel on the front of the tooth; mesenchymal Gli1⁺ stem cells feed the dentine-making side. (≈ 1 mm (loop region))
Periodontal ligament stem cells — A tooth root cut across: between the root’s cementum and the jaw’s alveolar bone runs the periodontal ligament, whose collagen fibres sling the tooth in its socket. Perivascular stem cells in the ligament can make new cementum, ligament and bone. (≈ 5 mm across)
Exfoliating baby tooth (SHED source) — A baby tooth being shed: its root is eaten away by odontoclasts as the permanent tooth grows beneath it. The pulp left in the fallen crown is a convenient source of stem cells (SHED). (≈ 1.5 cm)
Root apex: apical papilla and HERS — The open end of a growing tooth root: a cuff of epithelium, Hertwig’s epithelial root sheath, guides root shape, while the apical papilla beyond holds stem cells (SCAP) that become the odontoblasts of the root — the basis of regenerative root-canal treatment in young teeth. (≈ 3 mm (root apex))

Heart, kidney & other organs 14

Cardiac “stem cells”: the c-Kit debate — A block of heart muscle with the rare c-Kit⁺ interstitial cells once claimed to be cardiac stem cells. Lineage tracing showed they make almost no new muscle — most are endothelial or mast cells — and adult human cardiomyocytes renew slowly (about 1 % a year at 25) mainly by existing cells dividing. (≈ 200 µm across)
Epicardial progenitors after heart injury — The heart’s outer lining, the epicardium, is a sheet of progenitors in the embryo. After a heart attack it reactivates (WT1⁺, Tbx18⁺): cells thicken, undergo an epithelial-to-mesenchymal transition and migrate into the injured wall, becoming fibroblasts and vessel-wall cells rather than new muscle. (≈ 300 µm across)
Endothelial colony-forming cells — True endothelial progenitors from blood or cord blood: after one to three weeks in culture they grow out as tight, cobblestone-patterned colonies of endothelial cells (CD31⁺, VEGFR2⁺) that can form new blood vessels — unlike the “early EPCs”, which turned out to be blood cells. (≈ 2 mm colony)
Parietal epithelial cells as podocyte progenitors — A glomerulus cut open inside Bowman’s capsule: the flat parietal epithelial cells lining the capsule include CD24⁺ CD133⁺ progenitors, most numerous at the urinary pole, which in some settings can replace lost podocytes around the capillary tuft (or, when they overgrow, form scarring crescents). (≈ 200 µm across)
Kidney tubule repair after acute injury — A proximal tubule cut open after injury: dead cells slough into the lumen, and surviving tubular cells — not a dedicated stem cell — flatten, lose their brush border, switch on Sox9 and Kim-1, divide and then re-differentiate to restore the lining. (≈ 60 µm across)
Olfactory epithelium: horizontal and globose basal cells — The smell-sensing lining of the nose keeps making neurons for life. Globose basal cells (GBCs) divide to replace olfactory sensory neurons, whose cilia face the air; flat horizontal basal cells (HBCs, p63⁺) on the basement membrane are a reserve that rebuilds everything after severe injury. (≈ 60 µm thick)
Inner-ear supporting cells regenerating hair cells — A patch of sensory epithelium from the inner ear: mechanosensory hair cells with their staircase bundles sit in a mosaic of supporting cells. In birds and fish, when hair cells die, supporting cells divide or convert directly (switching on Atoh1) into new hair cells; in mammals this barely happens. (≈ 50 µm across)
Adrenal cortex renewal from the capsule — A wedge of the adrenal gland: Shh⁺ progenitors just under the capsule (signalling to Gli1⁺ capsule cells) feed the cortex, whose cells move inwards over months — through the zona glomerulosa, fasciculata and reticularis — and die at the border with the medulla. (≈ 1 mm across (mouse))
Pituitary Sox2⁺ stem cells (marginal zone) — A pituitary gland cut through the middle: Sox2⁺ stem cells line the cleft (a remnant of Rathke’s pouch) between the anterior and intermediate lobes and are scattered through the anterior lobe, where they renew hormone-producing cells and signal to them. (≈ 1 cm (human))
Urothelium and its basal progenitors — The bladder lining: a basal layer of small Krt5⁺, Shh⁺ cells, intermediate cells above, and huge, often two-nucleated umbrella cells on top, sealed with uroplakin plaques. After injury or infection the lining regrows quickly from its basal and intermediate progenitors. (≈ 50 µm thick)
Thymic epithelial progenitors — A thymus lobule cut open: a cortex packed with developing T cells on a meshwork of cortical epithelial cells, and a paler medulla with Aire⁺ medullary epithelial cells. Bipotent epithelial progenitors near the junction between them keep both networks going — and fade as the thymus shrinks with age. (≈ 2 mm lobule)
Fallopian tube secretory progenitors — A slice of the fallopian tube with its branching folds: the lining mixes multiciliated cells, which sweep the egg along, with PAX8⁺ secretory cells that act as the progenitors of both — and are thought to be where many high-grade serous ovarian cancers start. (≈ 1 mm across)
Taste bud renewal from Lgr5⁺ progenitors — A taste bud in the tongue’s lining: an onion-shaped cluster of about 50–100 elongated taste cells (types I, II and III) whose tips meet at the taste pore. They last only about ten days and are replaced from Lgr5⁺ / Krt14⁺ progenitors at the bud’s base and edges. (≈ 60 µm tall)
Adventitial progenitors of the artery wall — An artery cut across: the endothelium-lined intima, a thick media of smooth muscle and elastic laminae, and the outer adventitia with its own small vessels. Sca-1⁺ and Gli1⁺ progenitors in the adventitia can make smooth-muscle cells and fibroblasts — and feed thickening of the wall in disease. (≈ 1 mm across)

Niche principles & behaviour 18

Asymmetric stem cell division (niche and fate determinants) — One division, two fates: the stem cell keeps its grip on the niche cell (adherens junctions) and orients its spindle away from it. Polarity proteins (Par complex) gather on one side and fate determinants such as Numb on the other, so the daughter that stays receives niche signals and self-renews while the other leaves to differentiate. (≈ 20 µm)
Three ways a stem cell can divide — Stem cells can divide asymmetrically (one stem cell and one differentiating cell), symmetrically to expand (two stem cells, as in growth or repair) or symmetrically to differentiate (two committed cells). Tissues usually balance the pool by mixing these at the level of the population. (schematic, cells ≈ 10 µm)
Immortal strand hypothesis — Cairns’ immortal-strand idea (1975): when a stem cell divides, it might keep every chromosome’s older template DNA strand (dark) and pass the newly copied strands (light) to its differentiating daughter, protecting itself from copying errors. Evidence is mixed — in most tissues segregation looks random. (schematic, ≈ 15 µm)
Quiescence: leaving and re-entering the cell cycle — Many adult stem cells spend most of their lives outside the cycle in quiescence (G0), a reversible, actively maintained rest. Signals such as injury bring them first into an alert state and then back into G1 to copy their DNA (S), prepare (G2) and divide (M). (schematic)
Label-retaining cells (pulse–chase) — Find slow-cycling stem cells by dilution: label every nucleus (a pulse of H2B-GFP or BrdU), then wait. Each division halves the label, so after a long chase only cells that rarely divide stay bright — label-retaining cells. (≈ 150 µm field)
Competition for niche space — A niche has room for only so many stem cells. Here every slot is full: a fitter (for example, mutant) clone is expanding and pushing a neighbour out of its slot — the displaced cell loses niche signals and differentiates. This is how clones take over tissues. (≈ 60 µm)
Anatomy of a stem cell niche — The parts most niches share: a stem cell anchored to its niche cell and to the basement membrane, short-range signals (membrane-bound and secreted), nearby blood vessels and nerves, and immune cells — all of which tune whether it rests, divides or lets a daughter leave. (≈ 80 µm (schematic))
Notch lateral inhibition (salt-and-pepper fates) — In a sheet of equal progenitors, a cell that makes slightly more Delta activates Notch in all its neighbours, which then make less Delta themselves. The result is a salt-and-pepper pattern: scattered Delta-high cells take one fate (for example secretory or neural) and their Notch-active neighbours keep another. (≈ 100 µm patch)
Cytonemes delivering niche signals — Some niche signals travel along cytonemes — long, thin filopodia that reach from a signalling cell to its targets, several cell widths away, and hand over ligands such as Hedgehog or Wnt at their tips. (≈ 60 µm)
Primary cilium Hedgehog signalling — Quiescent stem cells sense Hedgehog through their single primary cilium. Without ligand, Patched sits in the cilium and keeps Smoothened out; when Hedgehog binds Patched, Patched leaves and Smoothened floods in, activating Gli transcription factors that travel to the nucleus. (≈ 5 µm cilium)
Matrix stiffness steers MSC fate — Engler’s experiment (2006): the same mesenchymal stromal cells placed on gels as soft as brain (≈1 kPa), muscle (≈10 kPa) or pre-bone (≈30 kPa) become branched neuron-like cells, spindle myoblast-like cells or spread, polygonal osteoblast-like cells. Stiffness pulls YAP/TAZ into the nucleus. (3 gels, cells ≈ 50 µm)
Cell shape steers fate on micropatterned islands — McBeath’s islands (2004): mesenchymal stromal cells confined to small adhesive squares stay round, low in tension and become fat cells; on large squares they spread, build stress fibres (high RhoA–ROCK tension) and become bone cells — shape alone tips the choice. (islands ≈ 1,000 and 10,000 µm²)
Oxygen gradients in a stem cell niche — Oxygen falls off quickly with distance from a vessel, shown here as nested shells around a capillary. Many stem cells sit in the low-oxygen zones, where HIF-1α stabilises, glycolysis dominates and quiescence is favoured; progenitors that divide hard sit closer to the blood supply. (≈ 100 µm across)
Young vs aged stem cell niche — The same niche young (left) and old (right). With age there are fewer and less active stem cells, some senescent cells appear, the basement membrane thins and the matrix stiffens with extra collagen, and inflammatory cells and signals build up — the niche itself ages along with its stem cells. (≈ 100 µm each)
Refilling an empty niche by dedifferentiation — Stem cell identity can be regained. When a niche slot falls empty, nearby committed daughters — here a chain of linked progenitors — break apart, move back into contact with the niche and become stem cells again, as seen in fly gonads and the mammalian gut. (≈ 50 µm)
Cell competition: winners and losers — In an epithelium, cells compare their fitness with their neighbours. A clone of “winner” cells (for example with more Myc) grows, and the less fit “loser” cells along its border are eliminated by apoptosis and pushed out — a quality control that can also help pre-cancerous clones spread. (≈ 120 µm patch)
Old mitochondria go to the differentiating daughter — When some stem-like cells divide, they sort their mitochondria by age: the daughter that remains a stem cell receives mostly young mitochondria (green), while older ones (red) go to the daughter that will differentiate (Katajisto and colleagues, 2015). (≈ 20 µm)
Mother centrosome stays with the stem cell — A germline stem cell dividing next to its hub: the older (mother) centrosome stays anchored near the niche contact and the stem cell keeps it, while the daughter centrosome goes to the cell that will differentiate — a pattern also seen in mouse radial glia. (≈ 15 µm)

Model organisms 5

Hydra and its three stem cell lineages — A freshwater Hydra, which seems not to age: every cell of its body column is constantly renewed. Its two epithelial layers are themselves stem cells, and multipotent interstitial (i-) cells between them make nerve cells, stinging-cell (nematocyte) nests, gland cells and gametes. (≈ 1 cm long)
Drosophila midgut intestinal stem cells — The fruit-fly gut lining: small Delta⁺ intestinal stem cells sit on the basement membrane next to the visceral muscle, each with a daughter enteroblast (Notch on, Su(H)⁺) that becomes a giant polyploid enterocyte — or an enteroendocrine cell (Prospero⁺) when signalling differs. (≈ 60 µm patch)
Drosophila neuroblast asymmetric division — A larval neuroblast divides very unequally: apical aPKC/Par proteins (pink) orient the spindle and push the fate determinants Miranda, Prospero and Brat (yellow) to the basal side, so the small ganglion mother cell that buds off inherits them and makes neurons, while the big neuroblast stays a stem cell. (≈ 12 µm neuroblast)
Planarian neoblasts in the parenchyma — A slice through a flatworm: dividing neoblasts (piwi-1⁺) fill the parenchyma between the gut branches but are absent from the head tip and pharynx. A single clonogenic neoblast transplanted into an irradiated worm can rebuild the whole animal. (≈ 1 mm wide (worm))
C. elegans seam cells: stem-like divisions — Along each side of a worm runs a row of seam cells that behave like stem cells: at every larval stage each divides asymmetrically — the front daughter fuses with the skin (hypodermis) while the back one stays a seam cell — steered by Wnt/β-catenin asymmetry and timed by heterochronic genes. (≈ 1 mm worm)

Lineage trees 24

Haematopoiesis lineage tree — The classic blood family tree: a self-renewing haematopoietic stem cell gives multipotent progenitors, then common myeloid and lymphoid progenitors, and finally every mature blood cell — each drawn with its real shape. (cells ≈ 7–60 µm (schematic tree))
Neural lineage tree — Neural stem cells make neuronal and glial progenitors: intermediate progenitors become neuroblasts and neurons, glial progenitors give astrocytes and oligodendrocyte precursors that myelinate axons. Microglia come from yolk-sac macrophages, not from this tree. (cells ≈ 10–100 µm (schematic tree))
Mesenchymal stromal cell lineages — A mesenchymal stromal (stem) cell in the centre with its classic fates around it: osteoblast to osteocyte, chondrocyte, adipocyte, myoblast to myotube, tenocyte-like fibroblast and smooth muscle. (cells ≈ 10–100 µm (schematic))
Haematopoiesis: revised (continuum) model — The newer view of blood formation: some stem cells make megakaryocytes almost directly, lymphoid-primed multipotent progenitors (LMPP) keep lymphoid and myeloid options, and lineage choice is gradual rather than a strict myeloid–lymphoid split. (cells ≈ 7–40 µm (schematic))
Lymphoid lineage tree — From the common lymphoid progenitor to T cells (helper, cytotoxic, regulatory), B cells and antibody-secreting plasma cells, NK cells and innate lymphoid cells. (cells ≈ 7–15 µm (schematic))
Myeloid lineage tree — The myeloid branch: granulocyte–monocyte progenitors give neutrophils, eosinophils, basophils and mast cells, and through monocyte–dendritic cell progenitors, monocytes, macrophages and conventional dendritic cells. (cells ≈ 10–25 µm (schematic))
Tissue-resident macrophage origins — Many tissue macrophages are laid down before birth: yolk-sac erythro-myeloid progenitors seed microglia, while fetal-liver monocytes give Kupffer cells, alveolar macrophages and Langerhans cells; adult blood monocytes refill gut and dermis. (cells ≈ 10–30 µm (schematic))
CD4 T-helper fates — A naive CD4 T cell, once activated, polarises into Th1, Th2, Th17, T follicular helper or regulatory T cells depending on the cytokines around it — each defined by a master transcription factor. (cells ≈ 7–12 µm (schematic))
Neural crest derivatives — The neural crest — a migratory population leaving the dorsal neural tube — gives sensory and enteric neurons, Schwann cells, melanocytes, adrenal chromaffin cells, and craniofacial cartilage and bone. (cells ≈ 10–100 µm (schematic))
Endoderm lineage tree — Definitive endoderm patterns into foregut, midgut and hindgut, then buds the liver, pancreas, lungs and thyroid, and lines the gut — shown down to typical mature cells. (cells ≈ 10–30 µm (schematic))
Ectoderm lineage tree — Ectoderm splits into surface ectoderm (epidermis, hair, lens), neural plate (neurons and glia of the brain and cord) and the neural crest at their border. (cells ≈ 10–100 µm (schematic))
Mesoderm lineage tree — Mesoderm becomes paraxial (somites: skeletal muscle, cartilage), intermediate (kidney) and lateral-plate mesoderm (heart, blood vessels, blood cells). (cells ≈ 7–100 µm (schematic))
Cardiac lineage tree — Cardiac mesoderm forms the first and second heart fields and the proepicardium: they make left- and right-ventricular, atrial and outflow-tract cardiomyocytes, pacemaker cells, and (through the epicardium) cardiac fibroblasts and coronary smooth muscle. (cells ≈ 10–100 µm (schematic))
Pancreatic lineage tree — PDX1+ pancreatic progenitors split into tip cells (acinar) and trunk cells (ductal and endocrine); NGN3+ endocrine progenitors then give the islet α, β, δ and PP cells. (cells ≈ 10–20 µm (schematic))
Retinal lineage (birth order) — A multipotent retinal progenitor makes the seven retinal cell classes in a conserved order: ganglion cells first, then cones, horizontal and amacrine cells, rods, bipolar cells and last Müller glia. (cells ≈ 10–200 µm (schematic))
Intestinal epithelial lineage — A crypt-base columnar (LGR5+) stem cell makes transit-amplifying cells that commit to the absorptive line (enterocytes) or the secretory line (goblet, Paneth, enteroendocrine and tuft cells). (cells ≈ 10–30 µm (schematic))
Airway epithelial lineage — Airway basal stem cells (KRT5, TP63) renew the lining: they make club (secretory) cells, which in turn give multiciliated and goblet cells, plus rare ionocytes, tuft and neuroendocrine cells. (cells ≈ 10–30 µm (schematic))
Epidermis and appendage lineages — Epidermal stem cells feed three compartments: the interfollicular epidermis (basal to spinous, granular and cornified cells), the hair follicle and the sebaceous gland. (cells ≈ 10–40 µm (schematic))
Kidney lineage tree — Intermediate mesoderm gives two founders: nephron progenitors (SIX2+) that make podocytes and the segments of the nephron, and the ureteric bud that branches into the collecting ducts. (cells ≈ 10–30 µm (schematic))
Germline lineage tree — Primordial germ cells migrate to the gonad and become pro-spermatogonia or oogonia; spermatogonial stem cells then make spermatocytes, spermatids and sperm, while oogonia enter meiosis as oocytes. (cells ≈ 10–100 µm (schematic))
Vascular and haemogenic lineages — Lateral-plate mesoderm makes angioblasts that become arterial, venous and lymphatic endothelium; a haemogenic endothelium buds off the first definitive blood stem cells. (cells ≈ 10–40 µm (schematic))
Trophoblast lineage tree — Trophoblast stem cells give villous cytotrophoblast, which fuses into the multinucleated syncytiotrophoblast or invades the uterine wall as extravillous trophoblast. (cells ≈ 10–100 µm (schematic))
Adipocyte origins: white, beige, brown — Brown fat cells share a MYF5+ dermomyotome origin with skeletal muscle, while white and beige adipocytes arise from PDGFRα+ precursors; beige cells appear in white fat on cold exposure. (cells ≈ 20–100 µm (schematic))
B-cell development and fates — In the marrow, pro-B and pre-B cells rearrange their antibody genes to become immature B cells; in lymphoid organs, mature B cells become follicular or marginal-zone cells, and after a germinal-centre reaction, plasma cells or memory B cells. (cells ≈ 7–15 µm (schematic))

Maturation sequences 17

Erythropoiesis: from pro-erythroblast to red cell — Red-cell maturation in order: the cell shrinks, its cytoplasm turns from blue (ribosomes) to pink (haemoglobin), the nucleus condenses and is pushed out, and the reticulocyte matures into a biconcave red cell. (cells ≈ 7–20 µm)
Granulopoiesis: myeloblast to neutrophil — Neutrophil maturation in the marrow: primary (azurophil) granules appear in the promyelocyte, specific granules in the myelocyte, and the nucleus indents (metamyelocyte), becomes a band and finally segments into lobes. (cells ≈ 10–20 µm)
Thrombopoiesis: megakaryocytes to platelets — A megakaryoblast duplicates its DNA without dividing (endomitosis), grows into a giant polyploid megakaryocyte, then extends beaded proplatelets that release platelets into the blood. (cells ≈ 2–100 µm)
Osteoclastogenesis on bone — Monocyte-lineage precursors settle on bone, respond to M-CSF and RANKL, fuse into multinucleated osteoclasts and seal onto the surface with a ruffled border to resorb it. (cells ≈ 10–100 µm)
Myogenesis: satellite cell to myofibre — Muscle regeneration step by step: a quiescent satellite cell activates, proliferates as myoblasts, differentiates, fuses into a myotube with central nuclei and matures into a striated myofibre with peripheral nuclei. (cells ≈ 10 µm – 1 mm)
Osteoblast differentiation to osteocyte — Skeletal progenitors commit (RUNX2), become pre-osteoblasts and matrix-laying osteoblasts (SP7/osterix), mineralise the osteoid and finally become osteocytes embedded in bone with long canalicular processes. (cells ≈ 10–50 µm)
Growth-plate chondrocyte maturation — In the growth plate, small resting chondrocytes become flattened proliferating cells stacked in columns, then swell into prehypertrophic and hypertrophic chondrocytes before the cartilage is replaced by bone. (cells ≈ 10–40 µm)
Adipogenesis: preadipocyte to fat cell — A spindle-shaped preadipocyte rounds up and switches on PPARγ and C/EBPα; many small lipid droplets appear and fuse until one droplet fills the cell and pushes the nucleus to the edge. (cells ≈ 20–120 µm)
Neurogenesis: radial glia to mature neuron — Radial glia divide to make intermediate progenitors; their daughters become migrating neuroblasts that sprout neurites, grow an axon and dendrites, and finally make synapses. (cells ≈ 10–300 µm)
Oligodendrocyte maturation and myelination — Bipolar oligodendrocyte precursors (PDGFRα, NG2) become highly branched pre-myelinating cells, then myelinating oligodendrocytes whose processes wrap compact myelin sheaths round several axons. (cells ≈ 10–100 µm)
Cardiomyocyte maturation — Heart-muscle cells mature from small, round, proliferating cells with scattered myofibrils into long rods with aligned sarcomeres, intercalated discs and often two nuclei — the gap stem-cell-derived cardiomyocytes still need to close. (cells ≈ 10–120 µm)
Spermatogenesis and spermiogenesis — A spermatogonium enters meiosis as a large primary spermatocyte (paired chromosomes), divides twice into round spermatids, which build an acrosome, condense and elongate the nucleus and grow a tail. (cells ≈ 5–20 µm (sperm ≈ 55 µm long))
Folliculogenesis: primordial to antral follicle — An oocyte grows inside its follicle: flat granulosa cells (primordial) turn cuboidal (primary), multiply into several layers with a zona pellucida (secondary), and a fluid-filled antrum forms (antral follicle). (follicles ≈ 30 µm – 2 mm)
Lens fibre differentiation — At the lens equator, cuboidal epithelial cells elongate enormously into hexagonal fibre cells packed with crystallins, then destroy their nuclei and organelles so the lens stays transparent. (fibres ≈ 5 µm wide, up to 10 mm long)
Photoreceptor maturation — A post-mitotic photoreceptor precursor grows an inner segment and a connecting cilium; stacked membrane discs then build up into the light-sensing outer segment. (cells ≈ 2 µm wide, ≈ 60 µm long)
Sebocyte holocrine maturation — Sebocytes move inward from the gland's rim, fill with lipid, lose their nucleus and burst — releasing the whole cell as sebum (holocrine secretion). (cells ≈ 10–30 µm)
Endothelial-to-haematopoietic transition — In the embryonic aorta, flat haemogenic endothelial cells switch on RUNX1, round up, bulge into the lumen and bud off as the first haematopoietic stem cells. (cells ≈ 10–20 µm)

Directed differentiation protocols 14

Neurons from hPSCs (protocols) — Directed differentiation of human pluripotent stem cells into neurons: choose spinal motor neurons, midbrain dopaminergic neurons, cortical neurons or sensory nociceptors — each with its stages, days and patterning factors, and the product drawn up close. (wells ⌀ ≈ 1 cm (cells enlarged))
Glia from hPSCs (protocols) — Directed differentiation into glial cells: astrocytes via neurospheres and glial progenitors, oligodendrocytes via OLIG2+ progenitors and OPCs, or microglia via yolk-sac-like haematopoiesis. (wells ⌀ ≈ 1 cm (cells enlarged))
Blood cells from stem cells (protocols) — Making blood cells in culture: haematopoietic progenitors through haemogenic endothelium, red cells from CD34+ progenitors, megakaryocytes and platelets, macrophages from embryoid bodies, or T cells on Notch-ligand stroma. (wells ⌀ ≈ 1 cm (cells enlarged))
Cardiomyocytes from hPSCs (Wnt modulation) — The widely used small-molecule protocol: a pulse of Wnt activation (CHIR99021) makes mesoderm, Wnt inhibition (IWP2) then specifies cardiac progenitors, and beating cardiomyocyte sheets appear around day 8. (wells ⌀ ≈ 1 cm (cells enlarged))
Pancreatic β cells (SC-islets) from hPSCs — The multi-stage route to stem-cell-derived islets: definitive endoderm, primitive gut tube, posterior foregut, PDX1/NKX6.1 pancreatic progenitors, NGN3 endocrine progenitors in 3D clusters, and finally insulin-secreting SC-islets with some α cells. (wells ⌀ ≈ 1 cm (cells enlarged))
Hepatocytes from hPSCs — Activin A makes definitive endoderm, BMP4 and FGF specify hepatic endoderm, HGF expands hepatoblasts, and oncostatin M with dexamethasone matures them into polygonal, often binucleate albumin-secreting hepatocyte-like cells. (wells ⌀ ≈ 1 cm (cells enlarged))
Lung alveolar type 2 cells from hPSCs — Anterior foregut endoderm (dual SMAD and TGF-β/BMP inhibition) is ventralised by Wnt, BMP4 and retinoic acid into NKX2-1+ lung progenitors, which form surfactant-producing alveolar type 2 cells in 3D alveolospheres. (wells ⌀ ≈ 1 cm (cells enlarged))
Retinal pigment epithelium from hPSCs — hPSCs pass through an eye-field stage (nicotinamide, Activin A), patches of pigment appear, and after enrichment a hexagonal, pigmented cobblestone RPE monolayer forms on a porous insert — as used in clinical RPE patches. (wells ⌀ ≈ 1 cm (cells enlarged))
Keratinocytes from hPSCs — Retinoic acid and BMP4 make surface ectoderm; keratinocyte progenitors (KRT14, TP63) expand, and lifted to an air–liquid interface they stratify into a cornifying epidermis. (wells ⌀ ≈ 1 cm (cells enlarged))
Melanocytes from hPSCs — Neural crest induction (Wnt activation with BMP4 and endothelin-3) makes SOX10+ crest cells that become MITF+ melanoblasts and pigmented, dendritic melanocytes. (wells ⌀ ≈ 1 cm (cells enlarged))
Endothelial cells from hPSCs — A short Wnt pulse makes lateral mesoderm; VEGF and forskolin specify vascular progenitors, and sorted CD31+/VE-cadherin+ cells form an elongated, cobblestone endothelial monolayer. (wells ⌀ ≈ 1 cm (cells enlarged))
Skeletal muscle from hPSCs — Wnt activation makes paraxial mesoderm, then FGF2 and HGF expand PAX7+ myogenic progenitors; on serum withdrawal they fuse into striated multinucleated myotubes. (wells ⌀ ≈ 1 cm (cells enlarged))
Podocytes from hPSCs — Wnt activation makes posterior intermediate mesoderm, FGF9 gives SIX2+ nephron progenitors, and BMP7 with retinoic acid and VEGF matures them into arborised podocytes with foot processes. (wells ⌀ ≈ 1 cm (cells enlarged))
Primordial germ cell-like cells (PGCLCs) — Human PSCs are first primed to incipient mesoderm-like cells (Activin A + CHIR); aggregated with BMP4, SCF, EGF and LIF they give round SOX17+/BLIMP1+ PGC-like cells inside floating aggregates — the start of in vitro gametogenesis. (wells ⌀ ≈ 1 cm (cells enlarged))

Stem-cell-derived cells 28

iPSC-derived cardiomyocyte monolayer — A beating sheet of stem-cell-derived cardiomyocytes: flattened, polygonal-to-elongated cells with myofibrils whose Z-bands give the striated look, joined by gap junctions so they contract together. (cells ≈ 30–100 µm)
Aligned cardiomyocytes on micro-grooves — Grown on a grooved or patterned surface, stem-cell-derived cardiomyocytes line up end to end and become longer, more rod-like and better striated — a common maturation trick. (cells ≈ 100 µm long)
iPSC-derived motor neurons — Large multipolar motor neurons with thick dendrites and long axons that bundle into fascicles — the cells studied in ALS and spinal muscular atrophy. (soma ≈ 30 µm, axons mm)
iPSC-derived dopaminergic neurons — Midbrain dopaminergic neurons with branched dendrites and long varicose axons studded with release sites (tyrosine hydroxylase+) — used to model Parkinson's disease. (soma ≈ 15–25 µm)
iPSC-derived cortical neuron network — A mature network of excitatory pyramidal neurons and inhibitory interneurons with interlacing dendrites, axons and synaptic boutons — the substrate for multi-electrode array and calcium-imaging studies. (soma ≈ 15–20 µm)
iPSC-derived sensory neurons — Round, pseudo-unipolar sensory neurons gathered in ganglion-like clusters with a T-shaped axon, each surrounded by flat satellite glia. (soma ≈ 20–50 µm)
iPSC-derived astrocytes — Star-shaped astrocytes with bushy processes and end-feet, the support cells that buffer ions and neurotransmitters and help build synapses (GFAP, S100β, AQP4). (cells ≈ 40–100 µm)
iPSC-derived microglia — Microglia-like cells in their two typical forms: ramified (surveying, fine branching processes) and amoeboid (activated, rounded and phagocytic). (cells ≈ 10–50 µm)
Oligodendrocytes myelinating nanofibres — Stem-cell-derived oligodendrocytes reaching out to an array of synthetic nanofibres (axon stand-ins) and wrapping them in segments of compact myelin — a test of myelination in a dish. (cells ≈ 50 µm; fibres ≈ 2 µm)
Neural rosettes (close-up) — Neuroepithelial cells radiating like petals around a central lumen — the dish version of the embryonic neural tube, with ZO-1 at the apical centre and dividing cells near it. (rosettes ≈ 100–200 µm)
Stem-cell-derived Schwann cells — Bipolar, spindle-shaped Schwann cells lining up side by side in parallel streams (S100, SOX10), as they do in the regeneration tracks of injured nerves. (cells ≈ 60–100 µm long)
Migrating neural crest cells — hPSC-derived neural crest cells streaming out of a neural aggregate: mesenchymal, motile cells with lamellipodia leading the way (SOX10, p75). (cells ≈ 30–60 µm)
RPE monolayer in side view — A row of retinal pigment epithelial cells on a porous membrane: tight-junctioned hexagonal cells with basal nuclei, apical melanin granules and long apical microvilli reaching up to photoreceptor tips. (cells ≈ 14 µm wide)
Stem-cell-derived photoreceptors — Rods and cones grown from stem cells standing on the dish, each with a synaptic terminal, cell body, inner segment and a stacked-disc outer segment (rods cylindrical, cones tapered). (cells ≈ 2 µm wide, ≈ 50 µm tall)
Stem-cell-derived retinal ganglion cells — Retinal ganglion cells with a compact dendritic arbor and one very long axon that, in the eye, forms the optic nerve (BRN3B, RBPMS) — studied for glaucoma. (soma ≈ 15 µm)
Stem-cell-derived hepatocytes with bile canaliculi — Polygonal, often binucleate hepatocyte-like cells packed side by side; between neighbours runs a network of tiny bile canaliculi, and glycogen fills the cytoplasm (albumin, CYP3A4). (cells ≈ 20–30 µm)
Stem-cell-derived smooth muscle cells — Spindle-shaped smooth muscle cells with cigar-shaped nuclei and long actin–myosin bundles, packed side by side in a "hill-and-valley" pattern (α-SMA, calponin). (cells ≈ 100–200 µm long)
iPSC-derived skeletal myotubes — Long, multinucleated myotubes made by fusion of myocytes, lined with sarcomere striations, with a few unfused mononuclear myoblasts between them. (myotubes ≈ 20 µm wide, 1 mm long)
Stem-cell-derived brown adipocytes — Thermogenic brown adipocytes with many small lipid droplets and mitochondria rich in UCP1, beside white adipocytes with one large droplet. (cells ≈ 20–40 µm (white up to 100 µm))
Osteoblasts on a mineralised nodule — A raised bone nodule built by stem-cell-derived osteoblasts: cuboidal cells on its surface lay down collagen (osteoid) that mineralises, and some become trapped inside as osteocytes. (nodule ≈ 0.5–1 mm)
Osteocyte network in matrix — Osteocytes embedded in a block of bone matrix (cut open), each in its lacuna and joined to neighbours by fine dendrites running through canaliculi — the mechanosensing network of bone. (osteocytes ≈ 10–20 µm)
Stem-cell-derived podocyte — A podocyte from kidney organoid or directed culture sitting on a capillary loop: primary processes branch into interdigitating foot processes that form the slit diaphragm (nephrin, podocin). (cell ≈ 20–30 µm)
Megakaryocyte shedding proplatelets — A large stem-cell-derived megakaryocyte with a lobulated polyploid nucleus extending long beaded proplatelet arms, from whose tips platelets break off. (cell ≈ 50–100 µm)
iPSC-macrophages eating beads — Stem-cell-derived macrophages spreading on the dish with ruffled edges and pseudopods, engulfing fluorescent beads or bacteria into phagosomes — a standard function test. (cells ≈ 20–40 µm)
Dendritic cells from monocytes — Monocytes cultured with GM-CSF and IL-4 become dendritic cells with long, thin veils (dendrites); with a maturation stimulus they cluster with T cells to present antigen. (cells ≈ 10–30 µm)
Osteoclasts resorbing a bone slice — Multinucleated osteoclasts (made from monocytes with RANKL and M-CSF) sealed onto a bone slice, leaving scalloped resorption pits as they move — the pit assay. (osteoclasts ≈ 50–100 µm)
Melanocyte feeding keratinocytes — An epidermal-melanin unit made from stem cells: one dendritic melanocyte passes melanosomes through its processes to many keratinocytes, which park them as caps over their nuclei. (melanocyte ≈ 50–100 µm span)
Stem-cell-derived inner-ear hair cells — Hair cells from inner-ear organoids standing among supporting cells, each topped by a staircase bundle of stereocilia with a single kinocilium — the sensors of sound and balance (MYO7A). (cells ≈ 10 µm wide)

Transdifferentiation (direct conversion) 1

Direct conversion (transdifferentiation) — Turning one specialised cell straight into another, with no pluripotent stage, by forcing a few lineage transcription factors: fibroblasts to neurons, cardiomyocytes, hepatocytes, endothelium, blood progenitors, oligodendrocyte precursors or chondrocytes; astrocytes to neurons; acinar or α cells to β cells; B cells to macrophages; and iris to lens in the newt. (cells ≈ 20–200 µm)

Dedifferentiation and plasticity 2

Dedifferentiation in regeneration — Mature cells stepping back to rebuild tissue: zebrafish cardiomyocytes take apart their sarcomeres and divide, newt muscle fibres break up into blastema cells, and Schwann cells become repair cells after nerve injury. (cells ≈ 20–100 µm)
Dedifferentiation and fate switching in tissues — Committed cells that revert or switch fate: airway club cells becoming basal stem cells, hepatocytes becoming biliary cells, β cells losing maturity in diabetes, and chondrocytes turning fibroblast-like in 2D culture. (cells ≈ 10–20 µm)

Fate landscapes and decisions 6

Waddington landscape — Waddington's epigenetic landscape: a marble (a pluripotent cell) rolls down branching valleys into stable differentiated fates. Settings add reprogramming (back up the hill), transdifferentiation (across a ridge) and dedifferentiation (back up the valley). (conceptual)
Waddington landscape from below (guy-ropes) — Waddington's 1957 view under the landscape: pegs (genes) are tied by guy-ropes (their products) to the underside, and the pull of the whole network shapes the valleys the cell rolls along. (conceptual)
Cell-state attractor landscape — A quasi-potential landscape seen from above: stable cell states sit in basins (attractors) separated by ridges, and transition paths link them — the modern, single-cell view of the Waddington picture. (conceptual)
Morphogen gradient (French flag) — Wolpert's French-flag model: a morphogen spreading from a source falls off with distance, and cells read concentration thresholds to adopt one of three fates in bands. (field ≈ 100 µm)
Neural tube dorsoventral patterning — A slice through the neural tube: SHH from the notochord and floor plate and BMP/WNT from the roof plate set up progenitor domains (dp1–6, p0–p3, pMN) — the code that motor-neuron protocols copy. (tube ≈ 200 µm)
Lineage tracing with a Cre reporter — Inducible Cre switches on a heritable reporter (e.g. tdTomato) in one stem cell; every descendant stays labelled, so the clone grows and later includes differentiated progeny — proof of what that cell makes. (clones ≈ 50–300 µm)

Fate cues and readouts 2

Multi-electrode array with stem-cell cardiomyocytes — A beating sheet of stem-cell-derived cardiomyocytes on an 8 × 8 grid of microelectrodes (cut back at one corner to show them), which record field potentials and conduction — a standard cardiotoxicity readout. (well ≈ 5 mm (cells enlarged))
Patch-clamp recording of an iPSC-derived neuron — A glass micropipette sealed onto the soma of a stem-cell-derived neuron to record its action potentials and currents — the test that a differentiated neuron is truly functional. (soma ≈ 15 µm)

Gut & stomach organoids 10

Small-intestinal organoid (enteroid) with crypt buds — A mini-gut grown from one Lgr5⁺ crypt stem cell in Matrigel: a central villus-like cyst with an inward-facing brush border, dead cells shed into the lumen, and crypt-like buds that hold the stem and Paneth cells. Cut open to show the columnar epithelium. (≈ 200–500 µm)
Colon organoid (colonoid) — A human colonic epithelial organoid. In differentiation medium (no Wnt) the wall thickens, goblet cells fill with mucin and mucus collects in the lumen; in expansion medium it stays a thin-walled cyst. (≈ 150–400 µm)
Gastric organoid (stomach) — A thin-walled stomach organoid from adult gastric stem cells: a large cyst of mucus-secreting pit cells with small gland domains, mucus inside the lumen. (≈ 200–800 µm)
Oesophageal organoid (stratified squamous) — A solid, layered organoid from oesophageal basal cells: dividing basal cells outside, flattening suprabasal layers, and a keratinised core — like the stratified lining of the oesophagus turned inside out. (≈ 150–300 µm)
Human intestinal organoid from iPSCs (HIO, with mesenchyme) — An iPSC-derived intestinal organoid: a folded, CDX2⁺ epithelial tube with villus-like ridges, surrounded by its own mesenchyme of fibroblasts and smooth-muscle cells. (≈ 1–3 mm)
Hindgut spheroids budding from endoderm — The start of the HIO protocol: a definitive-endoderm monolayer patterned with WNT and FGF forms CDX2⁺ hindgut spheroids that bud off and float, ready to be embedded in Matrigel. (field ≈ 600 µm)
Apical-out enteroid (reversed polarity) — An enteroid grown in suspension without matrix: it turns inside out so the brush border faces the medium, where microbes and drugs can reach it directly. (≈ 50–150 µm)
Organoid-derived monolayer on a membrane — Organoid cells opened out into a sheet on a porous Transwell membrane: tall columnar cells, goblet cells with mucin and a mucus layer on top, with both sides reachable for transport and infection studies. (patch ≈ 340 × 220 µm)
Freshly isolated intestinal crypts — Crypts released from mouse or human intestine with EDTA, ready to embed: U-shaped epithelial pockets with granular Paneth cells at the base and single cells around them. (crypt ≈ 50 × 150 µm)
Enteroid growth from a single stem cell (day 0–7) — One sorted Lgr5⁺ stem cell divides, closes into a hollow cyst by day 2–3 and starts budding crypts by day 5, giving a budding enteroid by day 7. (up to ≈ 300 µm)

Brain, eye & ear organoids 14

Cerebral organoid (whole, cut open) — A self-organising brain organoid grown from iPSCs in a spinning culture: translucent neuroepithelial buds over the surface, small pigmented patches and fluid-filled cysts; the cut shows ventricle-like cavities ringed by progenitor zones and a thin cortical plate. (≈ 2–4 mm)
Cortical organoid section with rosettes — A thin section through a cortical organoid: several ventricle-like rosettes, each ringed by SOX2⁺ radial glia, TBR2⁺ intermediate progenitors and an outer CTIP2⁺ neuron layer. (section ≈ 4 mm × 20 µm)
Neural rosette (radial glia around a lumen) — Close-up of one neural rosette: radial glial progenitors point their apical ends at a small central lumen, their nuclei at different heights (interkinetic nuclear migration) and round up to divide at the lumen; newborn neurons gather outside. (≈ 200 µm)
Forebrain assembloid (two fused spheroids) — Two region-specific brain spheroids placed side by side fuse within days: interneurons from the ventral (subpallial) half migrate into the cortical half, or axons project between cortex and thalamus or striatum. (≈ 2 × 1 mm)
Cortico-motor assembloid (cortex, spinal cord, muscle) — Three spheroids in a row: cortical neurons send axons to spinal motor neurons, which reach a skeletal-muscle spheroid and make it twitch — a whole motor pathway in a dish. (≈ 4 mm long)
Midbrain organoid with neuromelanin — A midbrain organoid grown for months makes dopaminergic neurons and dark neuromelanin granules like the human substantia nigra — used to model Parkinson’s disease. (≈ 1–2 mm)
Choroid plexus organoid with CSF-like cysts — A brain organoid patterned towards choroid plexus: ruffled epithelium secretes a cerebrospinal-fluid-like liquid into large, clear, fluid-filled cysts. (≈ 2–3 mm)
Retinal organoid (laminated, with photoreceptors) — An iPSC-derived retinal organoid: a phase-bright neural retina with a fuzzy brush border of photoreceptor outer segments in late culture, a pigmented RPE patch at one pole, and nuclear layers visible in section. (≈ 0.5–1.5 mm)
Optic cup self-formation (stages) — Embryonic stem-cell aggregates push out an optic vesicle that flattens and folds inwards into a two-layered optic cup — neural retina inside, presumptive RPE outside — as in the embryo. (each ≈ 300 µm)
Inner-ear organoid with hair-cell vesicles — Stem cells guided to otic fate form an aggregate holding small vesicles; their linings become sensory epithelia with hair cells carrying stereocilia bundles. (≈ 1 mm)
Neural tube organoid (dorsal–ventral domains) — A neural tube organoid with a slit-like central canal, patterned along its dorsal–ventral axis: floor plate at the bottom, OLIG2⁺ ventral progenitors and PAX7⁺ dorsal progenitors above. (≈ 300 µm long)
Air–liquid interface cerebral organoid slice (ALI-CO) — A cerebral organoid cut into a thick slice and grown on a membrane at the air–liquid interface: the core stays alive and long axon tracts grow out in bundles. (insert ⌀ 24 mm)
Vascularised brain organoid — A brain organoid with vessel-like tubes, made by switching on ETV2 in some cells so they become endothelium that branches over and into the tissue. (≈ 2 mm)
Brain organoid on a microelectrode array — A brain organoid sitting on the electrode grid of a multielectrode-array chip that records its spontaneous network bursts over months. (chip ≈ 14 mm (shown))

Kidney & bladder organoids 5

Kidney organoid with nephrons — An iPSC-derived kidney organoid: dozens of segmented nephrons — glomeruli with podocytes, proximal and distal tubules — joining a branching collecting-duct network in a soft stroma. (≈ 2–5 mm)
Kidney organoids at the air–liquid interface — Nephron-progenitor aggregates spread into flat organoids on a porous membrane insert, fed from below and exposed to air above — the standard format for kidney organoid culture. (insert ⌀ 24 mm)
Ureteric bud organoid (branching) — An organoid of the ureteric bud, the collecting-duct progenitor: it branches again and again in Matrigel, with RET⁺ cells packed in the swollen ampulla tips. (≈ 0.5–1 mm)
Nephron formation stages in an organoid — How each nephron forms: a renal vesicle becomes a comma-shaped then an S-shaped body, which fuses with the collecting duct; its lower limb cups into podocytes around an ingrowing capillary loop. (each ≈ 50–100 µm)
Bladder organoid (urothelium) — A bladder organoid of stratified urothelium: small basal cells outside, intermediate layers, and large umbrella cells lining the lumen with a uroplakin plaque. (≈ 200–500 µm)

Liver & pancreas organoids 7

Hepatocyte organoid (grape-like) — An organoid of proliferating hepatocytes: dense, grape-like clusters of large polygonal cells with small bile-canaliculus lumens rather than one big cavity. (≈ 200–500 µm)
Fatty liver (steatosis) organoid — A liver organoid loaded with fatty acids, or carrying a disease variant, fills with lipid droplets — a dish model of fatty liver disease (MASLD / NAFLD). (≈ 200–500 µm)
Cholangiocyte (bile-duct) organoids — Bile-duct organoids from adult liver: thin, clear cysts of one layer of cuboidal cholangiocytes that bud off one another. (≈ 100–600 µm)
iPSC liver bud (with endothelial network) — Hepatic endoderm from iPSCs, mixed with endothelial cells and mesenchymal stem cells, condenses on Matrigel into a liver bud laced with an endothelial network. (≈ 4–5 mm)
Hepato-biliary-pancreatic organoid — An organoid patterned along its length like the foregut–midgut boundary: liver at one end, pancreas at the other, a biliary domain between, all sharing one lumen. (≈ 1–2 mm long)
Stem-cell-derived islet (SC-islet) — A cluster of endocrine cells made from pluripotent stem cells: insulin-secreting β cells mixed with glucagon (α) and somatostatin (δ) cells, as in a human islet — or a β-cell core with an α-cell mantle, as in mouse. (≈ 100–200 µm)
Pancreatic progenitor organoid (folded) — Embryonic pancreatic progenitors in Matrigel grow into a folded, lobed epithelium around a branched lumen, with PDX1⁺ and SOX9⁺ progenitors. (≈ 300 µm)

Lung & airway organoids 3

Alveolosphere (alveolar organoid) — An alveolar organoid grown from type 2 alveolar stem cells with fibroblasts: plump SFTPC⁺ type 2 cells full of surfactant-storing lamellar bodies, and thin, flat type 1 cells forming the rest of the wall. (≈ 100–300 µm)
Airway organoid (bronchosphere) with cilia — An airway organoid from basal stem cells: pseudostratified epithelium with basal cells outside and multiciliated and mucus-secreting cells facing the lumen, where mucus collects. (≈ 200–500 µm)
Lung bud organoid (branching) — An early lung organoid from pluripotent stem cells: SOX2⁺ proximal stalks branching into swollen SOX9⁺ distal tips, as in the embryonic lung. (≈ 0.5–1 mm)

Gland & reproductive organoids 9

Branching mammary organoid — A mammary epithelial organoid branching in matrix: luminal ducts ending in bulbous tips, wrapped by a basket of contractile myoepithelial cells. (≈ 0.5–1 mm)
Polarised epithelial acinus (MCF10A in 3D) — Single breast epithelial cells in basement-membrane gel grow into a hollow, polarised acinus: nuclei on the outside, Golgi facing the central lumen, wrapped in laminin. (≈ 50–80 µm)
Prostate organoid (basal & luminal layers) — A prostate organoid with an outer layer of KRT5⁺ basal cells around androgen-receptor-positive luminal cells that line a lumen. (≈ 200–500 µm)
Endometrial gland organoids — Endometrial gland organoids respond to hormones like the womb lining: plain cysts when proliferating; folded walls and glycogen-rich secretions in the secretory phase. (≈ 100–400 µm)
Fallopian tube organoid (with cilia) — An oviduct organoid whose wall folds into the lumen like the tube’s mucosal folds, lined by multiciliated and PAX8⁺ secretory cells. (≈ 200–500 µm)
Thyroid follicle organoid — Stem-cell-derived thyrocytes arranged in hollow follicles that store thyroglobulin-rich colloid — the hormone-making unit of the thyroid. (≈ 200 µm)
Salivary gland organoid — A salivary gland organoid with branched ducts ending in clusters of secretory acini, like bunches of grapes. (≈ 300–600 µm)
Sweat gland organoid (coiled) — A sweat gland organoid: a tightly coiled secretory tubule wrapped in myoepithelial cells, opening into a straight duct. (≈ 100–200 µm)
In vitro ovarian follicle (alginate-encapsulated) — An ovarian follicle grown in a soft alginate bead: an oocyte with its zona pellucida, layers of granulosa cells, theca cells outside and, as it matures, a fluid-filled antrum. (≈ 150–400 µm)

Skin, hair, tooth & lens organoids 4

Skin organoid with hair follicles — A hair-bearing skin organoid from pluripotent stem cells: a cyst of stratified epidermis with keratin inside, a dermis around it, and hair follicles that sprout outwards and grow pigmented hairs. (≈ 2–4 mm)
Hair follicle germ (epithelial–mesenchymal) — A bioengineered hair follicle germ: an aggregate of keratinocytes pressed against an aggregate of dermal papilla cells; their contact makes a hair peg that grows a hair. (≈ 300–600 µm)
Bioengineered tooth germ — A tooth germ rebuilt from dental epithelial and mesenchymal cells: the epithelium folds into a cap (later a bell) over the condensed dental papilla, with an enamel knot signalling at its centre. (≈ 0.5–1 mm)
Lentoids (lens organoids) — Lens epithelial cells derived from stem cells pile up and differentiate into clear, crystallin-rich lens fibres, forming transparent, light-focusing lentoids. (each ≈ 0.2–1 mm)

Heart, muscle, bone & fat models 8

Cardioid (self-organising heart chamber) — A heart-chamber organoid from pluripotent stem cells: a beating wall of cardiomyocytes around a single cavity lined by endocardial cells, with an epicardial layer on the outside. (≈ 1–2 mm)
Engineered heart tissue between two posts — iPSC-derived cardiomyocytes in a fibrin gel cast around two flexible posts: the tissue compacts into a beating strip whose pull bends the posts, giving its contraction force. (strip ≈ 12 mm)
Biowire cardiac tissues — Cardiac tissues grown around a suture wire in microwells and matured with electrical pacing; the aligned tissue wraps the wire like a sleeve. (chip ≈ 3 cm)
Engineered skeletal muscle (myobundle) — Muscle stem cells in a fibrin/Matrigel gel anchored on a frame fuse into aligned, multinucleated myotubes that contract when stimulated. (≈ 1.5 cm)
Chondrogenic pellet in a conical tube — Mesenchymal stromal cells spun down into a pellet and fed TGF-β3 turn into a firm, glossy bead of cartilage at the bottom of a conical tube. (pellet ≈ 1–2 mm)
Bone (callus) organoid — A callus-like bone organoid: periosteal or stem cells aggregate, make hypertrophic cartilage and then mineralised bone nodules, as in fracture repair. (≈ 1–2 mm)
Bone marrow organoid — An iPSC-derived bone marrow organoid: stromal cells and sinusoid-like vessels form a niche where haematopoietic progenitors make myeloid, red-cell and megakaryocyte lineages. (≈ 1–2 mm)
Adipocyte spheroid (white or brown fat) — Fat-cell spheroids: white adipocytes each hold one big lipid droplet with the nucleus squeezed to the rim; brown adipocytes hold many small droplets and abundant mitochondria. (≈ 200–400 µm)

Blood-vessel & immune organoids 2

Blood vessel organoid (capillary network) — Pluripotent stem cells form a 3D network of capillaries in a collagen gel: endothelial tubes wrapped by pericytes and a basement membrane, like human microvessels. (≈ 0.5–1 mm)
Immune organoid on a membrane (tonsil or thymic) — Dense immune-cell aggregates on a membrane insert: tonsil organoids form germinal-centre-like B-cell clusters that make antibodies; artificial thymic organoids support T-cell development. (aggregate ≈ 1 mm)

Stem-cell embryo models 8

Blastoid (blastocyst-like model) — Stem cells self-organise into a blastocyst-like structure: a shell of trophectoderm-like cells around a cavity, with an inner cluster of epiblast-like and hypoblast-like cells. (human ≈ 150–250 µm)
Blastoid attaching to endometrial cells — An implantation model: a blastoid lands on a layer of endometrial cells with its polar trophectoderm first, and syncytiotrophoblast-like cells start to invade. (≈ 400 µm field)
Stem-cell-derived mouse embryo model (E8.5-like) — Embryonic, trophoblast and extra-embryonic endoderm stem cells together build an embryo model that reaches head folds, a beating heart, neural folds and somites inside a yolk-sac-like membrane. (≈ 1–2 mm)
Human peri-gastrulation embryo model — A complete human embryo model at about day 14: a bilaminar disc of epiblast over hypoblast, an amniotic cavity, a yolk sac and extra-embryonic mesoderm inside a trophoblast-like shell. (≈ 0.5 mm)
Post-implantation amniotic sac embryoid (PASE) — A lopsided cyst modelling the amniotic sac: flat amnion-like cells on one side, columnar epiblast-like cells on the other, and primitive-streak-like cells starting at the boundary. (≈ 150–200 µm)
Axioloid / somitoid (segmentation clock) — An elongating organoid of presomitic mesoderm that segments rhythmically: a HES7 clock wave sweeps towards the front, MESP2 marks the next boundary, and epithelial somites bud off. (≈ 0.5–1 mm long)
Trunk-like structure (neural tube with somites) — Mouse stem-cell aggregates in dilute Matrigel elongate into a trunk-like structure: a central neural tube flanked by rows of paired somites, with a tail-bud-like pole. (≈ 1 mm long)
Trophoblast organoid (placenta) — Placental trophoblast organoids grow "inside-out": cytotrophoblast outside, hormone-making syncytiotrophoblast inside, and invasive extravillous trophoblast sprouting outwards. (≈ 200–500 µm)

Domes, spheroids & culture formats 14

Matrigel domes in a 24-well plate — The everyday organoid culture: drops of basement-membrane extract set into domes on the floor of each well, each holding dozens of organoids, covered with medium. (12.8 × 8.6 cm)
Dome cross-section with organoids — A single dome cut through: organoids of many sizes, from small cysts to budding ones, held at different depths in the gel on the well floor, with medium above. (dome ⌀ ≈ 3–6 mm)
Plating organoids in domes (steps) — How domes are made: cells or crypt fragments are mixed with cold matrix and pipetted as drops, the plate is flipped so the drops set into domes at 37 °C, then medium is added. (well ⌀ ≈ 16 mm)
Hanging-drop spheroid culture — Cell suspensions hung as drops from the underside of a lid: gravity gathers the cells at the bottom of each drop into one spheroid (or embryoid body). (drop ≈ 20–30 µL)
Microwell array making uniform aggregates — A plate of tiny pyramid-shaped microwells: cells spun into it settle to the bottom of each pit and form thousands of aggregates of the same size. (pit ≈ 400–800 µm)
Miniaturised spinning bioreactor (12-well) — A 3D-printed lid turns a paddle in every well of a 12-well plate from one motor, keeping brain organoids suspended and well fed for months. (plate ≈ 12.8 × 8.6 cm)
Rotating wall vessel bioreactor — A fluid-filled vessel turning on its side keeps cell aggregates in gentle, continuous free fall (simulated low gravity), so they grow into large 3D tissues. (vessel ⌀ ≈ 5 cm)
Magnetic levitation of a spheroid — Cells tagged with magnetic nanoparticles are lifted by a magnet above the plate and gather into a spheroid that floats in the medium. (well ⌀ ≈ 16 mm)
Organoids in alginate microcapsules — Organoids grown inside small alginate capsules instead of animal-derived matrix — easy to handle in suspension and to scale up. (capsule ≈ 300–600 µm)
Passaging organoids (mechanical breaking up) — To expand organoids, the domes are dissolved and the organoids sheared through a narrowed pipette tip into fragments, each of which regrows into a new organoid. (tube ≈ 12 mm)
Microinjecting an organoid lumen — A fine glass needle delivers bacteria, toxins, drugs or dye straight into the closed lumen of an organoid — the side the gut, lung or stomach faces. (organoid ≈ 200 µm)
Organoid field in a dome (brightfield, top view) — What a dome looks like under the microscope: cystic organoids with bright rims and clear lumens, budding ones, and a few dark, dense ones that are dying. (field ≈ 600 × 400 µm)
Air–liquid interface organoid culture (inner dish) — Minced tissue in a collagen gel inside an insert sits on medium in an outer dish with its top open to air; epithelium and its native stroma grow together into cysts. (insert ⌀ ≈ 24 mm)
Organoid drug-screening plate (dose response) — Organoids seeded into a 96-well plate and treated with rising doses across the plate: they stay large at low doses and shrink and darken at high doses. (12.8 × 8.6 cm)

Air–liquid interface & barrier models 2

Airway epithelium at the air–liquid interface — Airway basal stem cells grown on a membrane with air above: they make a pseudostratified epithelium of ciliated, goblet and club cells under a layer of mucus. (patch ≈ 400 × 120 µm)
Blood–brain barrier model on a Transwell — iPSC-derived brain endothelial cells form a tight monolayer on the top of a membrane, with astrocytes and pericytes beneath to tighten the barrier. (patch ≈ 400 × 140 µm)

Organ-on-chip with stem-cell-derived cells 10

Intestine-on-chip with organoid-derived villi — Organoid cells line the upper channel of a stretchable two-channel chip and fold into villi under flow and rhythmic stretching; endothelium lines the lower channel, microbes can be added. (chip ≈ 2 cm (cut open))
Blood–brain barrier chip (perfused vessel) — A hollow channel through a gel lined with iPSC brain endothelial cells, wrapped by pericytes, with astrocytes in the surrounding gel. (chip ≈ 2 cm (cut open))
Liver-on-chip (sinusoid) — iPSC hepatocytes in the upper channel, sinusoidal endothelium below a porous membrane, with Kupffer and stellate cells — a perfused liver sinusoid for drug-toxicity tests. (chip ≈ 2 cm (cut open))
Perfused kidney tubule chip — A convoluted channel printed in a soft matrix and lined with proximal tubule cells, perfused through its lumen like a living nephron segment. (chip ≈ 3 cm)
Glomerulus-on-chip (podocytes) — iPSC-derived podocytes spread their foot processes over a membrane facing glomerular endothelium, forming a filtration barrier that holds back albumin. (chip ≈ 2 cm (cut open))
Heart-on-chip microtissues on micropillars — Rows of tiny cardiac tissues, each slung between two micropillars; every beat bends the pillars, which reads out the force. (chip ≈ 3 cm)
Multi-organ chip (body-on-chip) — Several organ models — liver spheroids, gut barrier, skin and a brain organoid — share one circulating medium driven by an on-chip pump. (chip ≈ 7.6 × 2.6 cm)
Three-lane chip: vessel sprouting into gel — A perfused endothelial tube grows against a gel lane held by phase guides; growth factors from the far lane make it sprout new vessels into the gel. (chip ≈ 3 cm)
Vascularised organoid on chip — An organoid placed in the middle chamber of a chip, where self-assembled vessels from the side channels grow in and connect, so medium flows through it. (chip ≈ 3 cm)
Morphogen-gradient chip patterning an organoid — A source and a sink channel set up a steady gradient of a signalling molecule across the gel, so cells along the organoid take different fates, as along an embryo’s axis. (chip ≈ 3 cm)

Bioprinted & engineered constructs 14

Organ building blocks with printed vessels (SWIFT) — Hundreds of thousands of organoids or spheroids packed into a dense living tissue; a sacrificial ink printed through it is washed out, leaving branching channels that can be perfused. (block ≈ 2.4 cm)
Bioprinted liver lobule pattern — Light-based printing places iPSC hepatic progenitors in hexagonal lobules with endothelial and supporting cells along the borders, like the liver’s own architecture. (lobule ≈ 0.6 mm)
Bioprinted skin (dermis + epidermis) — Layers of fibroblast-laden ink printed as a crosshatched dermis, then a layer of keratinocytes that stratifies into epidermis at the air–liquid interface. (patch ≈ 3 × 2 cm)
Bioprinted ear cartilage — An ear-shaped construct printed from chondrocytes or stem-cell-derived chondrocytes in a hydrogel, with visible print roads, to replace missing ear cartilage (microtia). (≈ 3 cm)
Bioprinted trachea — A printed tubular airway: a scaffold reinforced by rings of stem-cell-derived cartilage and lined inside by airway epithelial cells. (≈ 2.4 cm long)
Bioprinted miniature heart — A small heart printed inside a support bath from iPSC cardiomyocytes in a hydrogel made from the patient’s own tissue, with printed blood vessels. (≈ 2 cm)
Volumetric bioprinting in a rotating vial — A vial of cell-laden photoresin turns while light patterns are projected through it; where the doses add up, the gel sets, building a whole object in seconds. (vial ⌀ ≈ 16 mm)
FRESH printing in a gel support bath — Soft collagen and cell inks printed inside a bath of gelatin microparticles that holds each road in place until it sets; the bath melts away at 37 °C. (bath ≈ 4 cm)
Coaxial printing of hollow fibres — A nozzle within a nozzle prints a cell-laden shell around a sacrificial or crosslinking core, so the fibre comes out hollow — a ready-made vessel or tubule. (fibre ⌀ ≈ 1 mm)
Printed intestinal tube (bioprinting-assisted tissue emergence) — Intestinal stem cells printed as a line into a gel fuse and self-organise into one continuous tube with crypt-like buds and a shared, open lumen. (≈ 3 mm long)
Aspiration-assisted spheroid printing — A nozzle picks up one spheroid at a time by gentle suction and places it precisely into a gel, building rings and patterns of living tissue. (spheroid ≈ 400 µm)
Spheroids skewered on a needle array (Kenzan) — Spheroids threaded onto a bed of fine needles side by side; they fuse into a continuous tissue (for example a tube or patch) and the needles are removed. (needle pitch ≈ 400 µm)
Two-photon-printed niche cages (Nichoid) — Micro-cages printed with two-photon laser lithography give each stem cell a 3D niche of the right stiffness and spacing, helping it stay a stem cell. (cage ≈ 90 µm)
Gradient osteochondral construct — A plug for joint repair printed in layers: a porous bone phase seeded with stem-cell-derived osteoblasts, a calcified interface, and a cartilage phase on top. (⌀ ≈ 12 mm)

Imaging & analysis of organoids 8

Cleared whole organoid (3D fluorescence) — A brain organoid made transparent by tissue clearing, so labelled neurons, their processes and progenitor zones can be imaged right through it. (≈ 3 mm)
Light-sheet imaging of an organoid — An organoid in an agarose cylinder hangs in the light sheet: a thin plane of laser light from one objective, viewed at right angles by another, for fast, gentle 3D imaging. (chamber ≈ 4 cm)
Confocal z-stack of an organoid (optical sections) — A cystic organoid imaged as a stack of optical sections: each slice shows a ring of epithelium (E-cadherin) and nuclei (DAPI) around the lumen. (≈ 200 µm)
3D cell segmentation of an organoid — Image analysis outlines every cell of an organoid and gives each its own colour, ready for counting, sizing and tracking. (≈ 300 µm)
Lineage tracing in an organoid (Confetti clones) — Stem cells marked at random with one of four fluorescent colours each make a clone, seen as single-coloured ribbons that spread from the crypts. (≈ 300 µm)
Calcium imaging of a brain organoid — Neurons carrying a calcium sensor flash as they fire, showing network activity across the organoid surface. (≈ 2 mm)
Organoid sections on a slide — Organoids embedded, frozen or wax-embedded, cut into thin sections and stained on a glass slide under a coverslip. (slide 76 × 26 mm)
Spatial transcriptomics of an organoid section — An organoid section on a slide printed with barcoded capture spots: each spot reads the genes switched on beneath it, coloured here by cell-state cluster. (area ≈ 6.5 mm)

Disease models in organoids 10

Forskolin-induced swelling assay (cystic fibrosis) — Rectal organoids swell within an hour of forskolin as CFTR pumps fluid into the lumen; organoids from people with cystic fibrosis hardly swell — a test for which CFTR drugs will work. (≈ 100–300 µm)
Polycystic kidney disease organoid — Kidney organoids lacking PKD1 or PKD2 grow large, clear, fluid-filled cysts from their tubules — a dish model of polycystic kidney disease. (≈ 3–5 mm)
Microcephaly model: control vs affected brain organoid — Brain organoids infected with Zika virus, or lacking a microcephaly gene, end up much smaller, with fewer and thinner progenitor zones than controls. (≈ 1–3 mm)
SARS-CoV-2 infection of an airway organoid — Ciliated airway cells carrying ACE2 and TMPRSS2 become infected, shed virus into the lumen and die — organoids used to study COVID-19 and test antivirals. (≈ 300 µm)
Helicobacter pylori in a gastric organoid — Spiral H. pylori bacteria injected into the lumen of a gastric organoid swim to the mucus and attach to the pit cells, triggering inflammation. (≈ 300 µm)
Alzheimer’s disease brain organoid — Brain organoids carrying familial Alzheimer’s variants build up amyloid-β plaques between cells and phospho-tau tangles inside neurons. (≈ 2 mm)
Inflamed colonoid with immune cells — A model of inflammatory bowel disease: inflammatory cytokines thin the colonoid wall and make cells shed; macrophages and T cells added around it join in. (≈ 300 µm)
Enteric infection in a human enteroid — Human enteroids let researchers grow gut pathogens that need human cells: Cryptosporidium, human norovirus or rotavirus infecting the epithelium. (≈ 200 µm)
Glioma invading a cerebral organoid (GLICO) — Patient glioblastoma cells added to a cerebral organoid grow and spread through it along long tumour microtubes, as in the patient’s brain. (≈ 2–3 mm)
Engineered colorectal cancer progression in organoids — Gene editing of normal colon organoids step by step — APC, then KRAS, then TP53 and SMAD4 — reproduces the adenoma-to-carcinoma sequence, each step freeing growth from a niche factor. (each ≈ 200 µm)

Haematopoietic stem cell transplant 22

Bone marrow harvest from the iliac crest (cut-away) — A block cut through the back of the pelvis at the posterior iliac crest: skin, fat, the thin cortical shell and the red, spongy marrow inside. An aspiration needle passes through the cortex into the marrow and a syringe draws up dark marrow blood; earlier puncture tracks lie beside it. (≈ 4 cm block)
Bone marrow aspiration and biopsy needle — The hollow needle used to aspirate marrow and cut a core biopsy: a T-shaped handle, a cannula with a tapered, sharpened tip, the stylet (trocar) that fills it while it is pushed through bone, a probe to push the core out and the cylinder of marrow it cut. (≈ 10–15 cm long)
Marrow collection bag with in-line filters — The bag that receives a bone marrow harvest: marrow is pushed through two in-line filters (about 500 and 200 µm mesh) that hold back bone spicules and fat clumps, then collects in a large bag with anticoagulant before it is sent to the lab or straight to the recipient. (≈ 30 cm tall)
Stem cell mobilisation into the blood (G-CSF, plerixafor) — A marrow sinusoid cut open lengthwise. Stem cells are normally held in the niche by CXCL12 (SDF-1) on stromal cells binding their CXCR4 receptor; G-CSF loosens this and plerixafor blocks CXCR4, so stem and progenitor cells slip through the endothelium into the blood, from where they are collected by apheresis. (≈ 60 µm across)
Apheresis machine (stem cell collection) — A continuous-flow cell separator: blood drawn from one arm is spun in a centrifuge chamber under the lid, the band of mononuclear and stem cells is pumped into a collection bag and the rest goes back to the donor. Peristaltic pumps line the front panel; anticoagulant, plasma and collection bags hang from the pole. (≈ 1.4 m tall with its pole)
Apheresis separation channel (cut-away) — The ring-shaped channel spinning inside a cell separator, cut open: blood enters, and centrifugal force layers it by density — red cells against the outer wall, a thin creamy buffy coat of white and stem cells in the middle, golden plasma inside. The collection port sits at the buffy-coat interface. (≈ 25 cm across)
CD34⁺ cell selection with magnetic beads — Cells of an apheresis product next to a magnet: stem and progenitor cells carrying CD34 are coated with antibody-linked iron-oxide nanobeads and drawn towards the magnet, while untagged lymphocytes, granulocytes and red cells stay behind — the basis of CD34⁺ selection (and of T-cell depletion of grafts). (≈ 40 µm across)
Bone marrow through conditioning and engraftment — A slice across a marrow-filled bone through a transplant: the normal red marrow packed with blood-forming cells, the near-empty marrow after myeloablative conditioning (fat cells and dilated sinusoids left), donor cells settling in islands about two weeks after the infusion, and the refilled marrow once the graft has taken. (≈ 3 mm section)
Tunnelled central venous catheter (Hickman line) — The long-term central line used through a stem cell transplant for infusing the graft, chemotherapy, blood products and taking samples: two or three silicone lumens with colour-coded clamps and needle-free caps, joined to one catheter with a Dacron cuff that anchors in the skin tunnel. (≈ 60–90 cm long)
Homing of infused stem cells to the marrow — After a graft is infused, stem cells find their way into the marrow: from left to right a cell rolls along the sinusoid wall on E- and P-selectin, stops when CXCR4 meets CXCL12, squeezes between the endothelial cells, and settles in a niche beside the bone-lining osteoblasts below. (≈ 80 µm across)
Blood count recovery after a transplant (3D chart) — Counts after a stem cell transplant drawn as three ribbons: conditioning empties the marrow so neutrophils, platelets and lymphocytes fall to a low point (nadir) around the infusion on day 0; neutrophils recover first (engraftment when above 0.5 × 10⁹/L), then platelets, then lymphocytes. Peripheral blood grafts engraft fastest and cord blood slowest. (days −7 to +42)
Graft-versus-host disease in the skin — A block of skin from a transplant recipient with acute GvHD: donor T cells (blue) have crossed into the bottom (basal) layer of the epidermis, where keratinocytes die one by one — shrunken, bright pink apoptotic cells, often with a T cell beside them (satellite cell necrosis). In severe disease the epidermis splits from the dermis. (≈ 150 µm block)
Graft-versus-host disease in the gut (crypts) — Intestinal crypts cut open lengthwise in acute GvHD: donor T cells crowd the lamina propria and attack the crypt base, where the stem cells live; dying epithelial cells leave bubbly apoptotic bodies ("exploding crypt cells"), and in severe disease whole crypts drop out, leaving only a ghost of debris. (≈ 300 µm across)
Graft-versus-leukaemia effect — Why an allogeneic transplant can cure leukaemia: donor T cells and NK cells recognise the leftover leukaemic blasts as foreign and kill them. Large blasts with folded surfaces are surrounded by smaller donor lymphocytes; one blast is breaking up into blebs as it dies. (≈ 50 µm across)
HLA matching of donor and recipient — The tissue-type molecules (HLA) that decide who can donate: each person carries two sets (haplotypes) of HLA-A, -B, -C, -DRB1 and -DQB1, drawn here as coloured pegs on a donor and a recipient cell surface. A 10/10 match pairs every allele; a half-matched (haploidentical) relative shares one haplotype. (schematic)
Protective isolation room (transplant unit) — A single room on a stem cell transplant unit, cut open: HEPA-filtered air pours down over the bed from a ceiling panel and the room is kept at positive pressure behind a glass anteroom door, protecting a patient with almost no white cells. An infusion pump on its pole, a handwash basin and a chair complete it. (≈ 4 × 5 m room)
Thawing a frozen graft at the bedside — A cryopreserved stem cell bag is thawed quickly just before infusion: either in a 37 °C water bath, the bag sealed in a protective overwrap and gently kneaded until the last ice melts, or in a dry thawing device that warms it between heated plates — no water, so less risk of contamination. (≈ 40 cm across)
Infused stromal cells caught in lung capillaries — What happens to mesenchymal stromal cells given into a vein: at 15–30 µm across they are larger than the 5–8 µm alveolar capillaries, so most lodge at the first branches of the lung capillary net (first-pass effect) while flexible red cells slip past. (≈ 60 µm across)
Needles for injecting cells (end-hole, side-port, multi-port) — Cell injections need needles that do not shear or clump the cells: a plain bevelled end-hole needle, a closed-tip needle with side ports that sprays cells sideways into the tissue, and a multi-port needle that spreads them along its length — shown with their tips enlarged in front. (≈ 3–15 cm long)
Chimerism test: X/Y FISH after a sex-mismatched transplant — When donor and recipient are of different sexes, the origin of each blood cell can be read in its nucleus: fluorescent DNA probes light up the X chromosome (green) and Y chromosome (red), so after a female-to-male transplant donor cells show two green dots and the recipient’s own cells one green and one red. (≈ 60 µm field)
Mobilisation drugs for a stem cell donor (G-CSF and plerixafor) — What a donor or patient uses before stem cell collection: a box of prefilled G-CSF syringes injected under the skin once a day for four or five days, and a vial of plerixafor added if the cells do not come out into the blood well enough. (≈ 20 cm box)
Counting CD34⁺ cells by flow cytometry (3D plot) — How a stem cell collection is counted: each dot is one cell measured by a flow cytometer, placed by its CD45 brightness, CD34 brightness and size (side scatter). Stem cells form a small, separate cloud — CD34 bright, CD45 dim, small — whose share decides when there are enough to collect (often 2–5 million per kg). (thousands of cells)

Cord blood banking & donation 6

Umbilical cord blood collection (after birth) — Cord blood is collected after the baby is born and the cord clamped: the delivered placenta rests fetal side up in a stand with the cord hanging through it, a needle in the umbilical vein lets the blood drain by gravity into a collection bag with anticoagulant, which sits on a scale to record the volume. (≈ 22 cm placenta)
Cord blood volume reduction (layers in a press) — After centrifugation the cord blood bag has three layers — packed red cells at the bottom, a thin buffy coat with the stem cells, and plasma on top. A spring-loaded plasma press squeezes the plasma off into a satellite bag, leaving a small, concentrated buffy-coat product to freeze. (≈ 25 cm tall)
Cord blood freezing bag (two compartments) — A cord blood unit as it is frozen: a small flat bag divided by a heat seal into a larger (about 20 mL) and a smaller (about 5 mL) compartment, so part can be thawed for expansion or testing, with short sealed segments of tubing kept for identity and potency tests before release. (≈ 15 cm wide)
Cord blood bank storage room — Where cord blood units wait for a patient, sometimes for decades: a row of large vapour-phase liquid-nitrogen tanks fed through insulated piping from a bulk supply outside, an automated store that picks units robotically, oxygen-depletion alarms on the wall and a stainless filling hose. (≈ 6 × 5 m room)
Liquid-nitrogen dry shipper (cut-away) — How frozen stem cells travel between banks and hospitals: a dry shipper has no free liquid — liquid nitrogen is soaked into a porous absorbent lining, so it cannot spill, yet the well stays below −150 °C for a week or more. A canister holds the cassette; a data logger records the temperature; it all rides in a padded case. (≈ 50 cm tall)
Donor registry cheek-swab kit — How a volunteer joins a stem cell donor registry: four foam-tipped swabs are rubbed inside the cheeks, left to dry and sealed in a paper envelope with a consent form, then sent to a lab that reads the HLA type from the cheek cells. (≈ 20 cm envelope)

Gene-modified & engineered cells 11

Lentiviral gene transfer into a blood stem cell — Ex vivo gene therapy, one cell cut open: lentiviral vectors dock on a CD34⁺ stem cell and fuse with it; the cone-shaped capsids travel inward while the RNA is copied into DNA, enter the nucleus and the therapeutic gene is stitched into the chromosomes as a provirus that every daughter cell will inherit. (≈ 10 µm cell (virus enlarged))
Electroporation of CRISPR into a stem cell — How gene-editing tools get into blood stem cells: a brief electric pulse between two electrodes opens temporary pores where the field is strongest — the two poles of the cell facing the plates — and Cas9 protein loaded with its guide RNA (ribonucleoprotein, RNP) slips through before the membrane reseals. (≈ 10 µm cell (molecules enlarged))
Sickle cell blood before and after gene therapy — Red cells spread on a slide. Before treatment many cells of a person with sickle cell disease are rigid, crescent-shaped sickle cells; after gene therapy — a lentiviral anti-sickling globin gene or CRISPR editing that switches fetal haemoglobin back on — most red cells stay round, soft discs. (≈ 60 µm field)
Hypoimmune (HLA-edited) donor cell evading the immune system — Off-the-shelf cell therapies from donor or iPS cells are edited so the patient’s immune system ignores them: removing HLA molecules (B2M and CIITA knock-out) hides them from T cells, and extra CD47 tells NK cells and macrophages "don’t eat me". Unedited, a T cell grips the HLA on the surface; edited, the killers drift past. (≈ 40 µm across)
Chimeric antigen receptor (CAR) design, generation by generation — The parts of a CAR on a T- or NK-cell membrane: an antibody-derived scFv (heavy and light variable domains) that grips the tumour antigen, a hinge, a transmembrane anchor, then inside the cell one or two co-stimulatory domains (CD28, 4-1BB) and the CD3ζ chain with its three ITAM signalling motifs. Fourth-generation "armoured" CARs also release a cytokine such as IL-12. (schematic (a CAR ≈ 15 nm))
T cells activated on CD3/CD28 beads (CAR manufacturing) — The first step in making CAR-T cells: the patient’s T cells are mixed with magnetic beads about their own size coated with antibodies to CD3 and CD28. Clinging to the beads they switch on, grow into large blasts and begin to divide, ready for the CAR gene to be added; the beads are later pulled out with a magnet. (≈ 40 µm across)
CAR-T vein-to-vein journey (3D model) — The round trip of a personalised CAR-T therapy as a ring of small models: the patient’s white cells are collected by apheresis, shipped cold to a manufacturing site, activated and given the CAR gene, expanded in a bioreactor, tested, frozen and shipped back, then infused into the same patient after lymphodepleting chemotherapy. (about 3–5 weeks)
Safety switch: inducible caspase-9 in engineered cells — A built-in off switch for cell therapies: the cells carry an inactive caspase-9 fused to a drug-binding domain. If they cause harm (severe GvHD, toxicity), a small dimerising drug (rimiducid) pairs the molecules up, caspase-9 switches on and the engineered cells die by apoptosis within hours. Left: no drug; right: after the drug, the cell blebs and its nucleus breaks up. (≈ 30 µm across)
iPSC-derived CAR-NK cells attacking a tumour spheroid — Off-the-shelf natural killer cells made from engineered iPS cells and armed with a chimeric antigen receptor: they cluster on a small ball of tumour cells and grip it with their CARs. Each NK cell, cut open, shows its indented nucleus and the cytotoxic granules gathered towards the contact, ready to be released; dead tumour cells shrink and darken. (≈ 80 µm across)
Gene-corrected epidermal grafts on gauze carriers — Sheets of a patient’s own skin cells, grown from stem cells that were gene-corrected (as for junctional epidermolysis bullosa) or simply expanded (as for large burns): each thin, pale, translucent epidermal sheet is clipped to a petroleum-gauze carrier and shipped in a dish, ready to be laid onto the wound. (≈ 8 × 10 cm each)
Lentiviral provirus in the genome (schematic) — Where the therapeutic gene ends up after lentiviral gene therapy: a stretch of host DNA with the provirus stitched into it — long terminal repeats at both ends, an internal promoter, the therapeutic gene (for example a β-globin or ADA gene) and a regulatory element. Sites of insertion are tracked to check the safety of the treatment. (a few kilobases (DNA enlarged))

Mesenchymal stromal cell therapy 15

Hollow-fibre bioreactor expanding stromal cells (cut-away) — A closed, automated way to grow billions of mesenchymal stromal cells: thousands of porous hollow fibres run through a cartridge; cells attach to the inside of the fibres and are fed by medium flowing through them, while gases and waste cross the fibre walls to the outer circuit. (≈ 30 cm cartridge)
Stromal cells growing on a microcarrier bead — For large-scale culture, mesenchymal stromal cells grow spread out on the surface of microcarriers — beads about 0.2 mm across kept suspended in a stirred bioreactor. As they multiply they cover the bead and bridge to neighbouring beads; they are later released with an enzyme. (≈ 200 µm bead)
How stromal cells calm inflammation (paracrine signals) — Most benefit of mesenchymal stromal cell therapy comes from what the cells release rather than from becoming new tissue: a spread stromal cell sends out extracellular vesicles and soluble factors (PGE2, IDO, TSG-6, IL-10) that slow nearby T cells and turn inflammatory macrophages (M1, spiky) into repairing ones (M2, rounded). (≈ 80 µm across)
Mitochondria passing through a tunnelling nanotube — One way stromal cells rescue damaged cells: a thin membrane tube (tunnelling nanotube) forms between a stromal cell and an injured cell, and healthy mitochondria travel along it, restoring the energy supply of the recipient, whose own mitochondria are swollen and broken. (≈ 60 µm across)
Stromal cells injected into an arthritic knee — A knee cut through from front to back as cells are injected for osteoarthritis: the needle enters the joint space from the side, between the worn cartilage of the femur and tibia and the menisci, delivering a suspension of mesenchymal stromal (or marrow-concentrate) cells into the synovial fluid. (≈ 10 cm joint (section))
Stromal cells injected around a perianal fistula — A treatment for complex perianal fistulas in Crohn’s disease: the anal canal is cut in half to show the internal and external sphincters, a fistula tract running from the canal through the muscle to the skin, and the needle placing donor adipose-derived stromal cells into the tissue around the tract (and its internal opening) to help it heal. (≈ 6 cm section)
Bone marrow aspirate concentrate (point-of-care kit) — Marrow aspirated in theatre is spun in a small centrifuge in dual-chamber containers: red cells sink, plasma rises, and the thin nucleated-cell layer between them — with a few stromal and stem cells — is drawn off as a few millilitres of concentrate to inject into a joint, bone defect or tendon the same day. (≈ 40 cm centrifuge)
Adipose stromal vascular fraction (from lipoaspirate to cells) — Fat as a source of stromal cells: liposuction fluid collects in a canister and separates into oil, yellow fat and blood-tinged fluid; the fat is washed, digested with collagenase and spun, leaving the stromal vascular fraction — stromal cells, vessel cells and immune cells — as a small reddish pellet at the tip of a tube. (≈ 25 cm canister)
Donor cell fusing with a host liver cell — An explanation found for some early "transdifferentiation" results: a donor marrow-derived cell (green) fuses with a host hepatocyte, so the liver cell then carries a donor nucleus beside its own and makes donor proteins — it looked as if the stem cell had become a liver cell. (≈ 50 µm across)
Cell injection into a damaged Achilles tendon — The back of the ankle cut through lengthwise: the Achilles tendon running from the calf muscle to the heel bone has a thickened, degenerate patch (tendinopathy) where an ultrasound-guided needle places stromal cells or tenocyte-like cells among the disorganised fibres. (≈ 15 cm ankle (section))
Cell injection into a degenerated intervertebral disc — A lumbar disc cut through: with age or injury the jelly-like nucleus pulposus dries out and the ring of the annulus cracks, flattening the disc. A needle passed from the side into the nucleus places stromal or disc progenitor cells in a carrier, aiming to restore its water-holding matrix. (≈ 6 cm (section))
Cell injections into the calf for critical limb ischaemia — For legs whose arteries are blocked beyond the reach of surgery, marrow or stromal cells are injected in a grid of 30–40 small doses deep into the calf muscles, where they encourage new small vessels (collaterals) to grow; the skin is marked with the injection grid. (≈ 45 cm lower leg)
Steering iron-labelled cells with a magnet — Most cells injected into the blood never reach their target. Loading them with tiny iron-oxide particles lets an external magnet pull them out of the flowing blood and hold them against the vessel wall at the injured site, where more of them cross into the tissue. (≈ 1 mm tissue)
Infused stromal cells trapped in lung capillaries — The pulmonary first-pass effect: after intravenous infusion, mesenchymal stromal cells (about 16–20 µm across) are too large to pass the 6–7 µm alveolar capillaries, so most lodge where a precapillary vessel narrows, blocking it while red cells queue behind. Most of an intravenous dose is caught in the lungs within minutes. Vessel cut open. (cell ≈ 16–20 µm; capillaries ≈ 6–7 µm)
Apoptotic stromal cell engulfed by a macrophage — Why infused stromal cells work although they vanish within days: recipient cytotoxic cells kill them by perforin-dependent apoptosis, and phagocytes that engulf the apoptotic cells switch on indoleamine 2,3-dioxygenase and suppress the immune attack (shown in graft-versus-host disease). Stage: a killer lymphocyte attacking the stromal cell, or a macrophage engulfing the blebbing, phosphatidylserine-exposing remains. (≈ 30 µm)

Cell therapy for the eye 7

Routes for delivering cells into the eye — An eye cut in half along its axis with the three ways cells or gene therapies are delivered: into the vitreous jelly (intravitreal), under the retina where it is lifted into a bleb (subretinal, through a vitrectomy port), or into the thin space between sclera and choroid with a microneedle (suprachoroidal). (≈ 24 mm eye (section))
Implanting a stem-cell-derived RPE patch under the macula — Close-up of the back of the eye during surgery for macular degeneration: through a small cut in the retina (retinotomy) an injector slides a sheet of retinal pigment epithelium grown from stem cells — a single layer of dark hexagonal cells on a thin supporting membrane — into the space under the macula. The retina is cut away in front to show the patch beneath it. (≈ 6 × 3 mm patch)
Stem-cell-derived RPE monolayer on its scaffold (close-up) — What the cells in an RPE patch look like: a single layer of hexagonal retinal pigment epithelial cells joined by tight junctions, dark with melanin granules towards their top, a fringe of microvilli on the top surface (where photoreceptors would sit) and their bases on the thin porous membrane that carries them. (≈ 100 µm across)
Limbal stem cell graft restoring the cornea — For limbal stem cell deficiency (often after chemical burns), the clouded cornea — overgrown by conjunctiva and blood vessels — is cleared and a sheet of the patient’s own limbal epithelium, grown from a tiny biopsy of the healthy eye, is laid over it on amniotic membrane and sutured. Settings show the eye before, with the graft, and healed. (≈ 24 mm eye)
Injecting cultured corneal endothelial cells — A section through the front of the eye in a patient whose corneal endothelium has failed (the cornea swells and clouds): cultured donor endothelial cells are injected into the fluid-filled front chamber through the edge of the cornea; with the patient lying face down for a few hours they settle on the back of the cornea and take up its pumping job. (≈ 12 mm section)
Photoreceptor precursors grafted into a degenerated retina — A block of retina from an eye with retinitis pigmentosa, where the rods and cones are almost gone: transplanted photoreceptor precursors (green), made from stem cells, sit in the outer retina above the pigment epithelium and begin to grow the stacked outer segments that capture light, while connecting to the host bipolar cells. (≈ 100 µm section)
Encapsulated cell implant for the eye — A tiny sealed capsule of living engineered cells that releases a protective growth factor (ciliary neurotrophic factor, CNTF) for years: the semi-permeable hollow-fibre membrane lets nutrients in and the protein out but keeps immune cells away; cells grow on a scaffold of yarn inside, and a titanium loop sutures it to the white of the eye so it hangs in the vitreous. (≈ 6 mm capsule)

Cell therapy for the brain & spinal cord 9

Dopamine neuron graft for Parkinson’s disease — A slice across the brain at the level of the striatum: through a few needle tracks on each side, dopamine-producing neurons made from stem cells (or fetal tissue) are deposited into the putamen, the part of the striatum that has lost its dopamine supply; the grafts survive as small islands that reinnervate it. (≈ 14 cm brain slice)
Grafted dopamine neurons reinnervating the striatum — Inside a graft months after transplantation: clusters of dopamine neurons (tyrosine-hydroxylase positive) send fine, beaded axons out into the surrounding putamen, where they wind among the host’s medium spiny neurons and release dopamine from their swellings (varicosities). (≈ 300 µm across)
Neural stem cell graft bridging a spinal cord injury — A segment of spinal cord, cut lengthwise in half, after an injury has left a cavity: a graft of neural stem or progenitor cells in a supporting gel fills the gap, and regrowing axons (green) cross the bridge from the cord above towards the cord below, past the glial scar at the edges. (≈ 3 cm segment)
Transplanted oligodendrocyte cells remyelinating axons — Axons stripped of their myelin (as in multiple sclerosis or after spinal cord injury) conduct poorly. Transplanted oligodendrocyte progenitors mature into oligodendrocytes whose processes each wrap a fresh, thinner myelin sheath round a bare stretch of axon, re-forming the gaps (nodes of Ranvier) between sheaths. (≈ 60 µm across)
Intrathecal cell injection (lumbar puncture) — The lower back cut down the middle: a fine spinal needle passes between two lumbar spinous processes, through the ligaments and dura into the fluid-filled space around the nerve roots of the cauda equina, where cells (or gene therapy) are injected into the cerebrospinal fluid to spread along the spinal cord. (≈ 15 cm of spine (section))
Stereotactic frame for brain cell implantation — The frame that guides a cell-delivery cannula to a target deep in the brain with millimetre accuracy: a ring fixed to the skull by four pins, an arc on top with a carriage that sets the angle of entry, and the cannula passing through a small burr hole towards targets calculated from MRI. (≈ 30 cm frame)
Neural stem cells in a gel filling a stroke cavity — Brain tissue cut through a cavity left by a stroke: an injectable gel carrying neural stem cells fills the hole, giving them something to hold on to; the cells send processes into the surviving tissue around it while new blood vessels grow in from the border. (≈ 2 mm block (section))
Injecting cells straight into the spinal cord — For diseases such as ALS, cells are placed directly into the spinal cord: after removing the back of a few vertebrae (laminectomy) and opening the dura, a microinjector held on a frame over the cord lowers a fine cannula into the grey matter of the ventral horn, one level after another. (≈ 8 cm exposed cord)
Imaging a dopamine graft by PET (before and after) — Whether a dopamine-neuron graft is working can be seen with a PET scan: a tracer (such as ¹⁸F-DOPA) taken up by dopamine-making cells lights up the striatum. Before transplantation the putamen is dim; months after a graft, hot spots appear where the cells were placed. (≈ 15 cm brain slices)

Cell therapy for the heart 7

Cell therapy for an infarcted heart (injections or a patch) — After a heart attack a pale scar replaces part of the left ventricle. Cells can be injected straight into the muscle around it (the border zone) during surgery — each injection leaves a small raised deposit — or a sheet or patch of engineered heart muscle made from stem cells can be sutured over the scar on the outside of the heart. (≈ 12 cm heart)
Catheter injection of cells from inside the heart — Cells can be delivered without opening the chest: a catheter is passed up the aorta into the left ventricle, and a fine needle at its tip is pushed a few millimetres into the inside wall around the scar, guided by an electrical map of the muscle. The heart is cut through lengthwise to show the chambers. (≈ 12 cm heart (cut open))
Intracoronary infusion of cells (stop-flow balloon) — A coronary artery cut open lengthwise over the heart muscle: an over-the-wire balloon is inflated to stop the blood flow for a few minutes while cells are infused through its central channel downstream, so that they stay in the small vessels of the injured muscle long enough to cross into it. (≈ 3 cm of artery (section))
Engineered heart tissue strips on flexible posts — Heart muscle grown from stem cells for testing and repair: cardiomyocytes mixed with a fibrin or collagen gel compact into a strip slung between two flexible silicone posts in each well; as the tissue beats it bends the posts, and the movement measures its force. (≈ 2 cm well)
Cell-sheet engineering on a temperature-responsive dish — Dishes coated with a polymer that turns water-loving below 32 °C let a whole sheet of cells peel off intact, with its matrix and cell-to-cell junctions: cooled to 20 °C, the sheet lifts and curls from the edge; sheets lifted on a support membrane can be stacked into thicker tissue such as a heart-muscle patch. (≈ 3.5 cm dish)
Decellularised heart in a perfusion bioreactor — Detergent pumped through the coronary arteries washes every cell out of a donor heart, leaving a white, translucent ghost of its matrix with the vessels intact. Perfused with medium in a sealed jar, it can be reseeded with stem-cell-derived heart cells that settle into the empty scaffold (pink patches). (≈ 12 cm heart in a jar)
Grafted heart cells coupling with host muscle — At the edge of a cardiomyocyte graft: the host’s long, striated heart muscle cells lie in parallel; the smaller, less organised cells of the graft (green), made from stem cells, line up beside them and join through gap-junction plaques (connexin-43), so the electrical signal — and the beat — can pass between them. (≈ 150 µm across)

Regenerative therapies for other organs 18

Islet infusion into the liver’s portal vein — How donor islets — or islet-like clusters made from stem cells — are given for type 1 diabetes: they are dripped through a catheter into the portal vein, flow into its branches inside the liver and lodge in the small venules, where they pick up a blood supply and start making insulin. The liver is cut open to show the branching veins. (≈ 20 cm liver (section))
Encapsulation device with stem-cell-derived islet cells — A flat pouch implanted under the skin that holds clusters of insulin-making cells grown from stem cells: its porous membrane lets glucose, oxygen and insulin pass but keeps the immune system out (or, in open versions, lets blood vessels grow in). It is cut open to show the clusters inside. (≈ 4 cm pouch)
Autologous chondrocyte implantation into a cartilage defect — Repairing a hole in the cartilage of the knee with the patient’s own cells: chondrocytes taken from a small biopsy are grown on a collagen membrane, which is cut to the shape of the cleaned-up defect on the femoral condyle and glued in place with fibrin, smooth side up. (≈ 4 cm condyle)
Microfracture: marrow cells filling a cartilage defect (section) — A simpler way to bring repair cells into a cartilage hole: small holes punched with an awl through the bone plate at the bottom of the defect let marrow blood well up; the clot carries mesenchymal stromal cells that slowly fill the hole with fibrocartilage, softer than the original hyaline cartilage. (≈ 1.5 cm block)
Donor muscle cells restoring dystrophin (cross-section) — A cross-section of muscle in Duchenne muscular dystrophy after donor muscle precursor cells were injected: the fibres lack dystrophin under their membrane except where donor cells fused with them — those fibres show a ring of dystrophin (green) — clustered along the injection track. (≈ 1 mm bundle)
Regenerating the pulp of a tooth (cut-away) — Regenerative endodontics for an immature tooth whose pulp has died: after the root canal is disinfected, bleeding is provoked from beyond the open root tip (or a scaffold with dental pulp stem cells is placed), and the clot fills the canal; stem cells from the apical papilla grow in, forming new pulp-like tissue and thickening the root walls. (≈ 2.5 cm tooth)
Seeded scaffold bridging a segmental bone defect — A gap of several centimetres in a long bone that will not heal on its own: a 3D-printed lattice scaffold, seeded with the patient’s marrow stromal cells (or filled with marrow concentrate), is fitted into the gap and held by a locking plate and screws; new bone grows through the struts from both ends. (≈ 12 cm of femur)
Core decompression with marrow cells for a dying hip — Osteonecrosis of the femoral head, cut through: a wedge of dead bone under the joint surface has lost its blood supply. A drill track from the side of the femur relieves the pressure inside the bone and is filled with bone marrow concentrate, whose cells help new bone and vessels grow back into the dead area. (≈ 5 cm femoral head (section))
Bioartificial liver with hepatocyte spheroids — A bridge for liver failure: the patient’s plasma is separated from the blood and pumped through a column packed with spheroids of liver cells (from stem cells or cell lines), which take up toxins and make proteins, before it is returned. The column is cut open to show the packed spheroids. (≈ 40 cm circuit)
Seeded nerve conduit bridging a cut nerve — A gap in a peripheral nerve bridged by a tube: the two cut ends are sutured into a biodegradable conduit filled with a gel carrying Schwann cells or stem-cell-derived support cells, which guide regrowing axons from the upper stump across to the lower one. The conduit is cut open along its length. (≈ 3 cm conduit)
Tissue-engineered bladder dome (cut-away) — One of the first engineered hollow organs: a bladder-shaped biodegradable scaffold was seeded with the patient’s own bladder muscle cells on the outside and lining (urothelial) cells on the inside, grown in culture and then sewn onto the remaining bladder. A wedge is cut away to show the two layers. (≈ 8 cm)
Stem-cell-seeded tracheal graft — An engineered airway segment: a tube scaffold (decellularised donor trachea or a synthetic one) with rings of cartilage, seeded with the patient’s cells — chondrocytes in the rings and a lining of airway epithelium with cilia — and grown in a rotating bioreactor before implantation. Cut in half to show the layers. (≈ 6 cm segment)
Ear-shaped scaffold seeded with cartilage cells — For a child born without an outer ear (microtia): a porous, biodegradable scaffold in the shape of the opposite ear, made from a 3D scan, is seeded with the patient’s own cartilage cells, which grow through it before it is placed under the skin of the side of the head. (≈ 6 cm)
Tissue-engineered blood vessel in a pulsatile bioreactor — Growing a new artery: smooth muscle cells (or stem-cell-derived ones) are seeded on a tubular biodegradable mesh slipped over a silicone tube, and medium is pulsed through it like a heartbeat for weeks so the cells lay down strong, aligned collagen. The finished vessel can be decellularised and stored as an off-the-shelf graft. (≈ 30 cm chamber)
Cultured thymus tissue implanted in the thigh — For babies born without a thymus (complete DiGeorge syndrome), thin slices of donor thymus are cultured for a few weeks and then slipped into pockets in the thigh muscle. The patient’s own blood stem cells settle in them and mature into T cells, rebuilding the immune system over months. (≈ 6 cm muscle block)
Islets placed on the omentum in a biological scaffold — An alternative site to the liver for islet or stem-cell-derived islet grafts: islets mixed with the patient’s own plasma and thrombin form a gel on the surface of the omentum — the fatty, blood-rich apron in the abdomen — which is folded over them so they gain a blood supply quickly. (≈ 10 cm omentum)
Colon organoids transplanted onto an ulcer — A new approach for ulcerative colitis: organoids grown from a patient’s own healthy intestinal stem cells are delivered through a colonoscope onto an ulcer that will not heal, where they attach to the raw surface and spread into a new lining with crypts. (≈ 3 cm of colon (section))
Spermatogonial stem cell transplantation into the testis — A way to restore fertility after childhood cancer treatment: spermatogonial stem cells frozen before treatment are injected back into the testis through the rete testis; they travel into the seminiferous tubules, settle on the tubule walls and restart sperm production. (≈ 4 cm testis (section))

Cell manufacturing, testing & cryopreservation 10

Vertical-wheel bioreactor with stem cell aggregates (cut-away) — A single-use bioreactor made for fragile pluripotent stem cells: a large wheel turning on a horizontal axis in a U-shaped vessel mixes gently and evenly, keeping thousands of cell aggregates (about 0.2–0.3 mm across) in suspension with little shear. Cut open to show the wheel and aggregates. (≈ 15 cm vessel)
Counterflow centrifugation: washing and concentrating cells (cut-away) — Inside a closed cell-processing device: in a cone-shaped chamber spinning on a centrifuge, the outward pull on each cell is balanced against fluid pumped inwards. Large cells hold a fluidised bed in the chamber while small particles, platelets and old medium are washed out — a gentle way to wash or concentrate a cell product. (≈ 6 cm chamber)
Release testing of a cell therapy batch — Before a batch can be given to a patient it must pass its release tests, laid out here: aerobic and anaerobic blood-culture bottles for sterility, an endotoxin cartridge in its reader, mycoplasma PCR tubes, a flow cytometry tube for identity and purity, a cell count and viability slide, and the batch record with its certificate. (≈ 40 cm tray)
Chain of identity for a personalised cell therapy — With autologous products the right cells must reach the right patient: every bag, cassette and form carries the same unique identifier as the patient’s wristband, scanned and checked at collection, manufacture, shipping and finally at the bedside before infusion. (≈ 30 cm set)
What freezing does to a cell (slow, fast and with DMSO) — Why cells are frozen slowly with a cryoprotectant: cooled too fast, water cannot leave the cell in time and ice crystals form inside it, tearing it apart; cooled too slowly, ice grows outside and the cell shrinks badly in the concentrated salt. At about 1 °C a minute with DMSO the cell loses just enough water and survives, surrounded by ice outside. (≈ 40 µm across)
Vitrification device for stem cell colonies — Vitrification freezes cells so fast in strong cryoprotectant that the water turns to glass instead of ice: a tiny drop holding a few pluripotent stem cell colonies (or an embryo) is placed on the thin film tip of a device and plunged straight into liquid nitrogen, then covered with its protective cap. (≈ 15 cm with cap)
Automated dry thawing of a cryovial — A small instrument that thaws frozen vials of cells reproducibly without a water bath: the vial drops into a heated well, the instrument senses when the last ice has melted and stops, so every vial is thawed at the same rate — important when the cells are a medicine. (≈ 15 cm unit)
Cryostorage rack pulled from a liquid-nitrogen tank — Banked stem cells — master and working cell banks, cord blood or patient products — are kept in racks of boxes in the vapour above liquid nitrogen. Lifted out for a moment with cryogenic gloves on, the stainless rack steams and frosts over; each box position is logged in the inventory. (≈ 70 cm rack)
Automated stem cell culture workcell — Feeding, passaging and imaging pluripotent stem cells by robot inside a sterile enclosure: a robotic arm moves flasks and plates between a built-in incubator, a liquid handler and a microscope that checks each colony, so large batches are handled the same way every day. (≈ 2 m enclosure)
Adding cryoprotectant and filling freezing bags on a cold plate — The last manufacturing step before freezing: the cell product, cooled on a chilled plate, has cold freezing medium with DMSO added slowly by syringe while the bag is gently mixed, then it is divided into labelled freezing bags, the air pressed out and the tubing heat-sealed. (≈ 50 cm bench)

Regeneration models 12

Zebrafish heart regenerating after a cryoinjury — The zebrafish can regrow its heart: after the tip of the ventricle is frozen and dies, a fibrin and collagen scar forms, then surviving heart muscle cells near the wound dedifferentiate and divide, replacing the scar with new muscle within about two months. The heart is cut through to show ventricle, atrium and outflow bulb. (≈ 1.5 mm heart (section))
Newt lens regeneration from the iris — Remove the lens from an adult newt’s eye and a new one grows from the upper (dorsal) edge of the iris: pigmented iris cells lose their pigment, re-enter the cell cycle and form a small vesicle that thickens into a new lens — a classic case of transdifferentiation (Wolffian lens regeneration). (≈ 2 mm eye (section))
Mouse digit-tip regeneration (amputation level) — Mice — and children — can regrow a fingertip if it is cut beyond the base of the nail: a blastema forms under the nail and the last bone (third phalanx) regrows. Cut further back, in the joint region, the stump only heals with a scar. The toe is cut lengthwise to show bone, marrow and nail. (≈ 3 mm toe tip (section))
Ear-hole closure in the spiny mouse versus a lab mouse — A 4 mm hole punched through the ear shows a striking difference: the African spiny mouse (Acomys) fills it completely with new skin, cartilage, hair follicles and glands from a ring-shaped blastema, while an ordinary lab mouse only seals the edge with scar and the hole stays. (≈ 1.5 cm ear)
Deer antler regrowing each year (velvet antler) — The fastest-growing mammalian organ: each spring a deer casts its antlers and regrows them from stem cells in the periosteum of the pedicle — up to 2 cm a day — as soft, blood-rich bone covered in furry velvet skin, which hardens and is rubbed off by autumn. (≈ 1 m antlers)
Liver regrowth after partial hepatectomy (mouse) — The classic test of liver regeneration: two-thirds of a mouse liver (the median and left lobes) is removed; the remaining lobes enlarge as their cells divide, so within about a week the liver is back to its original mass, though not its original shape. The same happens after living-donor liver transplantation in people. (≈ 2 cm liver)
Tadpole tail regeneration (Xenopus) — A Xenopus tadpole regrows a cut tail — spinal cord, notochord, muscle and fin — in about a week, starting from a wound epidermis and a regeneration bud. Curiously, for a few days in mid-development (the refractory period) it cannot, which makes it a useful model for what switches regeneration on. (≈ 2 cm tadpole)
Müller glia rebuilding a zebrafish retina — In zebrafish (but not in mammals) the retina repairs itself: after light or toxic damage kills photoreceptors, Müller glia — the long support cells spanning the retina — re-enter the cell cycle, and each produces a column of neuronal progenitors that migrate to replace the lost cells. (≈ 150 µm section)
Hair cells regenerating in a zebrafish neuromast — Fish and birds regrow the sensory hair cells that people lose for good (one cause of deafness): in a lateral-line neuromast on the skin of a zebrafish larva, killed hair cells are replaced within two days as support cells around them divide and differentiate. Each hair cell carries a bundle with one long kinocilium. (≈ 40 µm organ)
Neoblasts: the planarian’s pluripotent stem cells (section) — A slice across a planarian flatworm: scattered through the loose tissue (parenchyma) between gut branches, nerve cords and the pharynx are small round neoblasts with a thin rim of cytoplasm — adult pluripotent stem cells, marked by piwi-1, that make up about a quarter of all cells and can rebuild a whole worm from a single cell. (≈ 1 mm wide section)
Inside an axolotl limb blastema (section) — A regenerating salamander limb cut lengthwise: under a thickened apical epithelial cap, a cone of dedifferentiated cells from the stump’s connective tissue, muscle and cartilage piles up into the blastema; nerves growing into it supply the signals it needs, and each cell remembers which part of the limb it came from. (≈ 2 mm)
Hydra regrowing a head — Cut a Hydra in half and the lower piece grows a new head in two or three days: a Wnt-driven organiser forms at the cut end, the tissue domes into a mouth cone (hypostome) and a ring of tentacles buds out. Hydra’s stem cells keep dividing for life, so it shows almost no ageing. (≈ 1 cm hydra)

Transplant & cell therapy in the clinic 3

Stem cell infusion on day 0 (bedside) — Transplant day: a patient lies in bed after conditioning while the thawed stem cell graft runs from a bag on the IV pole through the central line in the upper chest, with a pump controlling the flow and a dressing over the exit site. The people are built on the real human body (BodyParts3D). (real size (1 unit ≈ 50 cm))
Donating stem cells by apheresis — A donor, given G-CSF for a few days beforehand, reclines in a chair for three to four hours with a needle in each arm: blood is drawn from one, spun in the cell separator beside the chair to collect the stem cells, and returned to the other arm. The people are built on the real human body (BodyParts3D). (real size (1 unit ≈ 50 cm))
Bone marrow harvest in the operating theatre — A marrow donor lies face down under general anaesthesia; through small punctures over the back of the pelvis, aspiration needles draw marrow from both posterior iliac crests into syringes, which are emptied into the collection bag on the trolley beside the table. The people are built on the real human body (BodyParts3D). (real size (1 unit ≈ 50 cm))

Tissue engineering bioreactors 6

Decellularised lung being reseeded (ventilated bioreactor) — A donor lung stripped of its cells leaves a pale, see-through scaffold of airways, alveoli and vessels. Mounted with cannulas in its trachea and pulmonary artery, it is perfused with medium and gently ventilated while airway epithelial and vascular cells, often from stem cells, are reintroduced. (≈ 25 cm lungs)
Printing skin cells straight onto a wound — In situ bioprinting: a handheld printer rolls out a bio-ink of the patient’s skin cells or stromal cells in a gel directly onto a burn or wound, laying down a dermal layer and then an epidermal layer that follow the wound’s shape. (≈ 20 cm handheld printer)
Stretch bioreactor training an engineered tendon — Tendon and ligament cells line up and lay down strong collagen only when pulled: a gel or fibre construct seeded with stromal cells is clamped at both ends in a medium-filled chamber, and a motor stretches it a few per cent, many times a minute, for days. The close-up strip shows the spindle-shaped cells aligned along the pull. (≈ 15 cm chamber)
Perfusion bioreactor growing bone in a scaffold (cut-away) — Cells deep inside a thick scaffold starve in a dish. In a perfusion bioreactor medium is pumped through the pores of a bone scaffold seeded with stromal cells, feeding cells throughout and giving them the gentle fluid shear that pushes them towards bone; cut open here to show the flow through the struts. (≈ 5 cm chamber)
Rotating-wall vessel bioreactor with tissue constructs — A cylinder filled completely with medium turns slowly on its horizontal axis, so the cell-seeded constructs or aggregates inside are kept falling gently through the medium without ever settling — "simulated microgravity" with very low shear — while oxygen enters through a central membrane core. (≈ 12 cm vessel)
Cell banking tiers: master, working and product — How a cell line used for therapy is kept consistent for decades: one fully tested master cell bank of a few hundred vials is made first; each working cell bank is grown from a single master vial, and every manufacturing batch starts from one working-bank vial — drawn as trays of vials stepping down to product bags. (schematic)