Böhmig Georg A, Diebold Matthias, Budde Klemens
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, University of Basel, Basel, Switzerland.
Transpl Int. 2024 Nov 26;37:13475. doi: 10.3389/ti.2024.13475. eCollection 2024.
Based on promising results obtained in primate models, pioneers in the US have now started to explore the new frontier of genetically-edited pig-to-human transplantation. The recent transition of xenotransplantation into clinical medicine has included transplants in brain-dead subjects and the compassionate use of xenotransplants in living recipients without options for allotransplantation. While the barrier of hyperacute rejection seems to be successfully overcome by gene editing of donor pigs, the occurrence of accelerated rejection could pose significant limitations to the success of the procedure. Ultimately, the establishment of efficient and safe strategies to overcome immunologic barriers will, among other critical factors, such as potential xenozoonotic disease transmission or physiological differences, determine whether and for which indications xenotransplantation will be viable. Considering preliminary outcomes of compassionate use xenotransplantions, which may raise questions about how faithfully data from non-human primate models translate into human outcomes, further research in decedents may be necessary before proceeding with additional clinical transplants. Looking ahead, designing systematic trials in xenotransplantation, including the definition of acceptable eligibility criteria for such high-risk transplants, will be an immense challenge, especially in kidney transplantation, where dialysis provides an effective alternative to transplantation in most cases.
基于在灵长类动物模型中取得的良好结果，美国的先驱者们现已开始探索基因编辑猪到人的移植这一新领域。异种移植最近向临床医学的转变包括在脑死亡受试者身上进行移植，以及在没有同种异体移植选择的活体受者中同情性使用异种移植。虽然通过对供体猪进行基因编辑似乎已成功克服了超急性排斥反应的障碍，但加速排斥反应的发生可能会对该手术的成功造成重大限制。最终，建立有效且安全的策略来克服免疫障碍，将与其他关键因素（如潜在的异种动物疾病传播或生理差异）一起，决定异种移植是否可行以及适用于哪些适应症。考虑到同情性使用异种移植的初步结果，这可能会引发关于非人类灵长类动物模型的数据在多大程度上能如实转化为人类结果的疑问，在进行更多临床移植之前，可能有必要对死者进行进一步研究。展望未来，设计异种移植的系统试验，包括为此类高风险移植定义可接受的入选标准，将是一项巨大挑战，尤其是在肾脏移植方面，因为在大多数情况下透析为移植提供了一种有效的替代方案。
