Xenotransplantation Research -the Nonhuman Primate Model Is Preferable to the Human Decedent Model.

Abstract

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.