Cooper D K C, Mou L, Cleveland J D, Simmons J H, Cleveland D C
Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Transpl Int. 2025 Aug 7;38:14452. doi: 10.3389/ti.2025.14452. eCollection 2025.
Over the past 40 years, the pig-to-nonhuman primate organ transplantation model has enabled progress in xenotransplantation to be made to the point that we are now carrying out initial US FDA-approved clinical experiments on "compassionate" grounds. More recently, the pig-to-human brain-dead decedent model was introduced with claims that this might replace (or at least augment) the pig-to-NHP model. There are, however, several limitations of the decedent model, most notably the very limited period during which the subject may remain sufficiently metabolically and hemodynamically stable to allow meaningful monitoring of the fate of a pig organ graft. It will be exceedingly difficult to provide the regulatory authorities with data from experiments in which truly prolonged graft function has been monitored, whereas this is already being achieved in the pig-to-NHP model. In view of the complications related to the effects of brain death, the data obtained from xenotransplantation experiments in decedents may provide confusing results. There is a real risk that this may influence the regulatory authorities to become overly cautious in approving formal clinical trials of pig organ xenotransplantation to be initiated. We conclude that experiments in human decedents will be unable to replace studies in pig-to-NHP models.
在过去40年里，猪到非人灵长类动物的器官移植模型推动了异种移植取得进展，以至于我们现在正在基于“同情”理由开展美国食品药品监督管理局（FDA）批准的初步临床试验。最近，引入了猪到脑死亡人类死者的模型，据称这可能会取代（或至少补充）猪到非人灵长类动物的模型。然而，死者模型存在几个局限性，最明显的是受试者在代谢和血流动力学方面保持足够稳定以允许对猪器官移植命运进行有意义监测的时间非常有限。要向监管机构提供监测到真正延长的移植功能的实验数据将极其困难，而在猪到非人灵长类动物模型中已经能够做到这一点。鉴于与脑死亡影响相关的并发症，从死者异种移植实验中获得的数据可能会提供令人困惑的结果。确实存在这样的风险，即这可能会影响监管机构在批准启动猪器官异种移植正式临床试验时变得过于谨慎。我们得出结论，在人类死者身上进行的实验将无法取代在猪到非人灵长类动物模型中的研究。
