POINT OF VIEW
Transpl. Int.
Volume 38 - 2025 | doi: 10.3389/ti.2025.14452
This article is part of the Special IssueEuropeans and XenotransplantationView all 18 articles
Commentary/Personal Viewpoint XENOTRANSPLANTATION RESEARCH -THE NONHUMAN PRIMATE MODEL IS PREFERABLE TO THE HUMAN DECEDENT MODEL
- 1Center for Transplantation Sciences, Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States
- 2Shenzhen Xenotransplantation Medical Engineering Research and Development Center, The First Affiliated Hospital of Shenzhen University, Shenzen, China
- 3Children's Hospital of Los Angeles, Los Angeles, California, United States
- 4Michale E. Keeling Center for Comparative Medicine and Research, University of Texas MD Anderson Cancer Center, Bastrop, Louisiana, United States
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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. More recently, the pig-to-human brain-dead decedent model was introduced with claims that this might replace the pig-to-NHP model.There are, however, several limitations of the decedent model. Brain death can be associated with (i) immune cell infiltration into the graft, (ii) a systemic inflammatory response, and (iii) a limited period during which the subject may remain sufficiently metabolically and hemodynamically stable to allow meaningful monitoring of a pig organ graft. It will therefore be difficult to provide the regulatory authorities with data from experiments in which truly prolonged graft function, i.e., months or years, 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 risk that this may influence the regulatory authorities to become overly cautious in approving formal clinical trials of pig organ xenotransplantation. We conclude that experiments in human decedents will be unable to replace studies in pigto-NHP models.
Keywords: Kidney, Xenotransplantation, Brain death, decedent, nonhuman primate
Received: 05 Feb 2025; Accepted: 22 Jul 2025.
Copyright: © 2025 Cooper, Mou, Cleveland, Simmons and Cleveland. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: David K.C. Cooper, Center for Transplantation Sciences, Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States
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