Xenotransplantation Research Center, Seoul National University, College of Medicine, Seoul, South Korea.
Department of Microbiology and Immunology, Seoul National University, College of Medicine, Seoul, South Korea.
Xenotransplantation. 2024 Mar;31(2):e12850. doi: 10.1111/xen.12850.
Porcine islet xenotransplantation has been highlighted as an alternative to allo islet transplantation. Despite the remarkable progress that has been made in porcine-islet pre-clinical studies in nonhuman primates, immunological tolerance to porcine islets has not been achieved to date. Therefore, allo islet transplantation could be required after the failure of porcine islet xenotransplantation. Here, we report the long-term control of diabetes by allogeneic pancreatic islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets. Four diabetic male rhesus monkeys received the porcine islets and then allo islets (5700-19 000 IEQ/kg) were re-transplanted for a short or long period after the first xeno islet rejection. The recipient monkeys were treated with an immunosuppressive regimen consisting of ATG, humira, and anakinra for induction, and sirolimus and tofacitinib for maintenance therapy. The graft survival days of allo islets in these monkeys were >440, 395, >273, and 127, respectively, similar to that in allo islet transplanted cynomolgus monkeys that received the same immunosuppressive regimen without xeno sensitization. Taken together, it is likely that prior islet xenotransplantation does not affect the survival of subsequent allo islets under clinically applicable immunosuppressants.
猪胰岛异种移植已被视为同种胰岛移植的替代方案。尽管在非人类灵长类动物中进行的猪胰岛临床前研究取得了显著进展，但迄今为止尚未实现对猪胰岛的免疫耐受。因此，在猪胰岛异种移植失败后，可能需要进行同种胰岛移植。在这里，我们报告了在先前排斥的猪胰岛移植后，同种异体胰岛移植可长期控制糖尿病恒河猴的糖尿病。4 只糖尿病雄性恒河猴接受了猪胰岛，然后在首次异种胰岛排斥后，进行短期或长期的同种胰岛（5700-19000IEQ/kg）再移植。受者猴子接受了包括 ATG、humira 和 anakinra 用于诱导，以及 sirolimus 和 tofacitinib 用于维持治疗的免疫抑制方案。这些猴子的同种胰岛移植物存活天数分别为>440、395、>273 和 127，与未进行异种致敏且接受相同免疫抑制方案的同种胰岛移植食蟹猴相似。综上所述，异种胰岛移植前不太可能影响随后同种胰岛在临床应用的免疫抑制剂下的存活。
