Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
Department of Renal Transplant Surgery, Aichi University School of Medicine, Nagakute, Japan.
Am J Transplant. 2024 Apr;24(4):520-525. doi: 10.1016/j.ajt.2023.12.020. Epub 2023 Dec 28.
Brain-dead human subjects (decedents) were recently introduced as a potential preclinical experimental model in xenotransplantation. Brain death is associated with major pathophysiological changes, eg, structural injury and cell infiltration in vital organs, and major hormonal, metabolic, inflammatory, and hemodynamic changes. In 2 of the 3 initial experiments, the design of the experiments resulted in little or no new information becoming available. In the third, the experiment was unfortunately unsuccessful as neither of the 2 pig kidneys transplanted into the decedent functioned adequately. Failure may well have been associated with the effects of brain death, but an immune/inflammatory response to the xenograft could not be excluded. Subsequently, 2 further pig kidney transplants and 2 pig heart transplants have been carried out in human decedents, but again the data obtained do not add much to what is already known. In view of the profound changes that take place during and after brain death, it may prove difficult to determine whether graft failure or dysfunction results from the effects of brain death or from an immune/inflammatory response to the xenograft. A major concern is that, if the results are confusing, they may impact decisions relating to the introduction of clinical xenotransplantation.
脑死亡的人体受试者（死者）最近被引入异种移植的潜在临床前实验模型。脑死亡与主要的病理生理变化有关，例如，重要器官的结构损伤和细胞浸润，以及主要的激素、代谢、炎症和血液动力学变化。在前三个实验中的两个中，实验设计导致几乎没有新信息可用。在第三个实验中，实验不幸失败了，因为移植到死者体内的两个猪肾都没有充分发挥功能。失败很可能与脑死亡的影响有关，但不能排除对异种移植物的免疫/炎症反应。随后，在人类死者中又进行了两次猪肾移植和两次猪心移植，但再次获得的数据并没有增加太多已经知道的内容。鉴于脑死亡期间和之后发生的深刻变化，可能很难确定移植物衰竭或功能障碍是由于脑死亡的影响还是对异种移植物的免疫/炎症反应所致。一个主要的担忧是，如果结果令人困惑，它们可能会影响与临床异种移植引入相关的决策。
