Department of Surgery, Division of Transplantation, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Department of Pathology, Nippon Medical School, Tokyo, Japan.
Nat Commun. 2024 Apr 18;15(1):3361. doi: 10.1038/s41467-024-47679-6.
Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials.
异种移植代表了解决器官短缺危机的一种可能方案，并且随着猪到非人灵长类动物（NHP）心脏和肾脏大型动物模型中长期异种移植物存活，以及最近在人类遗体和临床研究中的短期成功，异种移植即将成为临床现实。然而，鉴于已发表的存活率不一致，以及临床前获取和免疫抑制与临床护理标准之间的关键差异，人们仍然对这些结果的安全临床转化存在担忧。值得注意的是，在没有 CD40/CD154 共刺激阻断的情况下，没有任何关于猪到 NHP 实体器官异种移植的研究能够实现超过一个月的异种移植物存活，而 CD40/CD154 共刺激阻断目前不是 FDA 批准的免疫抑制策略。我们现在提供了猪到 NHP 肾脏异种移植连续病例中的一致存活数据，包括在异种移植物冷藏时间超过 3 小时后的长期存活，以及使用 FDA 批准的免疫抑制的长期存活。这些数据为临床肾脏异种移植的安全性和可行性提供了关键的支持证据。此外，没有 CD40/CD154 共刺激阻断的长期存活可能为首次人体临床试验中考虑的免疫抑制方案提供重要见解。
