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categories: ["bodies"]categories: ["bodies"]tags: ["regenerative medicine", "transplantation", "stem cells", "chimeras", "immunology", "organ shortage"]tags: ["regenerative medicine", "transplantation", "stem cells", "chimeras", "immunology", "organ shortage"]summary: "The attempt to produce whole transplantable organs from cells rather than donors, currently limited to simple tissues, islet clusters and organs grown inside host animals."summary: "The attempt to produce whole transplantable organs from cells rather than donors, currently limited to simple tissues, islet clusters and organs grown inside host animals."updated: "2026-07-27"updated: "2026-08-23"humanEvidence: "Engineered skin, corneal and thymus tissue are approved and implanted in patients, and small trials of stem-cell-derived islets have produced insulin independence; no solid vascularized organ has been transplanted into a person."humanEvidence: "Engineered skin, corneal and thymus tissue are approved and implanted in patients, and small trials of stem-cell-derived islets have produced insulin independence; no solid vascularized organ has been transplanted into a person."access: "Only the simple tissues can be obtained: skin, limbal and thymus products are approved in some countries, stem-cell-derived islets are trial-only, and no solid organ is purchasable at any price."access: "Only the simple tissues can be obtained: skin, limbal and thymus products are approved in some countries, stem-cell-derived islets are trial-only, and no solid organ is purchasable at any price."reversibility: "difficult"reversibility: "difficult"issues: ["The islet insulin-independence results are stated without a citation.", "The 2025 hypoimmune islet case is described without a source."]------ ```infobox```infoboxlines 36–49 → 35–5517 unchanged lines not shown
The functional distinction is between organs that are essentially sheets or clusters and organs that are perfused three-dimensional structures with an arterial inlet and a venous outlet.The functional distinction is between organs that are essentially sheets or clusters and organs that are perfused three-dimensional structures with an arterial inlet and a venous outlet. The first category has clinical products. Cultured epidermal grafts, engineered skin, cultured limbal epithelium for corneal repair, and allogeneic cultured thymus tissue for children born without a thymus are all approved somewhere. Stem-cell-derived pancreatic islet clusters, which are [[organoids]] in construction if not in name, have produced insulin independence in most participants of small type 1 diabetes trials, using standard immunosuppression — arguably the first case of a lab-grown endocrine organ doing an organ's job in a person, even though it is delivered as a suspension of cell clusters into the portal vein rather than as an anatomical pancreas.The first category has clinical products. Cultured epidermal grafts, engineered skin, cultured limbal epithelium for corneal repair, and allogeneic cultured thymus tissue for children born without a thymus are all approved somewhere. Stem-cell-derived pancreatic islet clusters, which are [[organoids]] in construction if not in name, have produced insulin independence in most participants of small type 1 diabetes trials, using standard immunosuppression[^reichman2025] — arguably the first case of a lab-grown endocrine organ doing an organ's job in a person, even though it is delivered as a suspension of cell clusters into the portal vein rather than as an anatomical pancreas. The second category — kidney, liver, heart, lung — has nothing. Each requires on the order of ten to a hundred billion cells of several types, arranged around a branching vascular tree fine enough that no cell sits more than a couple of hundred micrometres from a capillary, with mechanical properties that survive arterial pressure and a surface that does not clot.The second category — kidney, liver, heart, lung — has nothing. Each requires on the order of ten to a hundred billion cells of several types, arranged around a branching vascular tree fine enough that no cell sits more than a couple of hundred micrometres from a capillary, with mechanical properties that survive arterial pressure and a surface that does not clot. ## Route one: build it## Route one: build it The constructive route seeds cells onto a scaffold and cultures the result. Purely synthetic scaffolds have worked for hollow, low-metabolic-demand structures — bladder, urethra, vaginal tissue — and not for solid organs, for the reasons set out in [[tissue-engineering]] and [[organ-bioprinting]]. The uterus falls on the far side of that boundary, being muscular and heavily perfused, which is why the only route to a working one remains a donated organ and the procedure described in [[uterus-transplantation]].The constructive route seeds cells onto a scaffold and cultures the result. Purely synthetic scaffolds have worked for hollow, low-metabolic-demand structures — bladder, urethra, vaginal tissue — and not for solid organs, for the reasons set out in [[tissue-engineering]] and [[organ-bioprinting]]. > [!caution] "Worked for hollow structures" describes case series, not a replicated result> The bladder claim rests on seven patients reported in 2006. When the same autologous cell-seeded scaffold was carried into a phase 2 study in children and adolescents with spina bifida, it improved neither bladder compliance nor capacity at 12 or 36 months, and serious adverse events of bowel obstruction or bladder rupture occurred in four participants; the investigators concluded that the safety record surpassed an acceptable standard.[^joseph2014]> Engineered airway grafts, the other line of this work to reach patients, ended in retracted papers and institutional findings of scientific misconduct.> Neither failure was a vascularization failure, which is the obstacle usually named: one construct did not reproduce its own earlier case series, and the other reached patients ahead of the animal evidence that would have predicted the outcome. The uterus falls on the far side of that boundary, being muscular and heavily perfused, which is why the only route to a working one remains a donated organ and the procedure described in [[uterus-transplantation]]. The variant with the strongest results uses a donor organ stripped of its cells as the scaffold, retaining the vascular tree in place of trying to fabricate one. Perfusing a detergent through the vasculature of a rat heart leaves an acellular matrix that can be reseeded with cardiac cells and stimulated to beat; the same approach has been applied to rodent lung and kidney, with reseeded kidneys producing dilute urine when perfused.[^ott2008][^song2013] These constructs functioned at a small percentage of native capacity for hours. Scaling the approach to human-sized organs runs into incomplete re-endothelialization, which causes thrombosis, and into the sheer number of cells required. This route is treated in detail in [[decellularized-scaffolds]].The variant with the strongest results uses a donor organ stripped of its cells as the scaffold, retaining the vascular tree in place of trying to fabricate one. Perfusing a detergent through the vasculature of a rat heart leaves an acellular matrix that can be reseeded with cardiac cells and stimulated to beat; the same approach has been applied to rodent lung and kidney, with reseeded kidneys producing dilute urine when perfused.[^ott2008][^song2013] These constructs functioned at a small percentage of native capacity for hours. Scaling the approach to human-sized organs runs into incomplete re-endothelialization, which causes thrombosis, and into the sheer number of cells required. This route is treated in detail in [[decellularized-scaffolds]]. ## Route two: grow it in an animal## Route two: grow it in an animallines 69–75 → 75–8119 unchanged lines not shown
An autologous organ, made from the patient's own reprogrammed cells, should escape rejection, but takes months to produce, costs a great deal per patient, and inherits the patient's genome — including whatever mutation caused the organ failure, unless it is corrected by [[somatic-gene-therapy]] first. Autologous manufacture is also incompatible with acute failure, where the patient has days, and a bespoke product priced per patient raises the distribution questions collected under [[access-and-inequality]].An autologous organ, made from the patient's own reprogrammed cells, should escape rejection, but takes months to produce, costs a great deal per patient, and inherits the patient's genome — including whatever mutation caused the organ failure, unless it is corrected by [[somatic-gene-therapy]] first. Autologous manufacture is also incompatible with acute failure, where the patient has days, and a bespoke product priced per patient raises the distribution questions collected under [[access-and-inequality]]. An allogeneic organ made from a banked cell line is manufacturable and immediately available, and needs immunosuppression like any transplant. The route being pursued to avoid that is hypoimmune engineering: deleting the genes required for surface expression of class I and class II major histocompatibility complex, and overexpressing CD47 so that natural killer cells and macrophages do not attack the resulting cells for lacking MHC. The approach was established in mice and in human cells before it reached patients.[^deuse2019] A 2025 report described hypoimmune-modified donor islet cells surviving and secreting insulin in a person with type 1 diabetes who received no immunosuppression, at short follow-up. That is early single-patient evidence rather than a demonstration of durable tolerance. Whether cloaked cells remain safe over years is unresolved, since the same modifications that hide a transplant from immune surveillance would also hide a tumour arising from it.An allogeneic organ made from a banked cell line is manufacturable and immediately available, and needs immunosuppression like any transplant. The route being pursued to avoid that is hypoimmune engineering: deleting the genes required for surface expression of class I and class II major histocompatibility complex, and overexpressing CD47 so that natural killer cells and macrophages do not attack the resulting cells for lacking MHC. The approach was established in mice and in human cells before it reached patients.[^deuse2019] A 2025 report described hypoimmune-modified donor islet cells surviving and secreting insulin in a person with type 1 diabetes who received no immunosuppression, at short follow-up.[^carlsson2025] That is early single-patient evidence rather than a demonstration of durable tolerance. Whether cloaked cells remain safe over years is unresolved, since the same modifications that hide a transplant from immune surveillance would also hide a tumour arising from it. ## Outlook## Outlook lines 92–97 → 98–10616 unchanged lines not shown
[^ott2008]: `paper` Ott, H. C. et al. "Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart." *Nature Medicine*, 2008. {A rat heart reseeded with rat cells, generating a small fraction of normal pump function for hours in a bioreactor rather than in an animal.}[^ott2008]: `paper` Ott, H. C. et al. "Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart." *Nature Medicine*, 2008. {A rat heart reseeded with rat cells, generating a small fraction of normal pump function for hours in a bioreactor rather than in an animal.}[^song2013]: `paper` Song, J. J. et al. "Regeneration and experimental orthotopic transplantation of a bioengineered kidney." *Nature Medicine*, 2013.[^song2013]: `paper` Song, J. J. et al. "Regeneration and experimental orthotopic transplantation of a bioengineered kidney." *Nature Medicine*, 2013.[^joseph2014]: `paper` Joseph, D. B. et al. "Autologous cell seeded biodegradable scaffold for augmentation cystoplasty: phase II study in children and adolescents with spina bifida." *Journal of Urology*, 2014. {The trial of the commercialised version of the 2006 bladder work. The authors conclude that it improved neither compliance nor capacity, and that the serious adverse events surpassed an acceptable safety standard.}[^reichman2025]: `paper` Reichman, T. W. et al. "Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes." *New England Journal of Medicine*, 2025. {An interim, non-prespecified phase 1–2 analysis. Ten of twelve full-dose participants were off exogenous insulin at day 365, all on immunosuppression; two participants died of unrelated causes.}[^carlsson2025]: `paper` Carlsson, P.-O. et al. "Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression." *New England Journal of Medicine*, 2025. {One participant, twelve weeks. The cells were gene-edited primary donor islets injected into forearm muscle, not cells grown from stem cells, so it tests immune cloaking rather than tissue manufacture.}[^kobayashi2010]: `paper` Kobayashi, T. et al. "Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells." *Cell*, 2010.[^kobayashi2010]: `paper` Kobayashi, T. et al. "Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells." *Cell*, 2010.[^yamaguchi2017]: `paper` Yamaguchi, T. et al. "Interspecies organogenesis generates autologous functional islets." *Nature*, 2017.[^yamaguchi2017]: `paper` Yamaguchi, T. et al. "Interspecies organogenesis generates autologous functional islets." *Nature*, 2017.[^wu2017]: `paper` Wu, J. et al. "Interspecies chimerism with mammalian pluripotent stem cells." *Cell*, 2017. {Human cells contributed at very low frequency and the chimeric pig embryos were assessed in early gestation, not carried to term.}[^wu2017]: `paper` Wu, J. et al. "Interspecies chimerism with mammalian pluripotent stem cells." *Cell*, 2017. {Human cells contributed at very low frequency and the chimeric pig embryos were assessed in early gestation, not carried to term.}removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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