Long‐term porcine islet graft survival in diabetic non‐human primates treated with clinically available immunosuppressants

Abstract

Although pancreatic islet transplantation is becoming an effective therapeutic option for patients with type 1 diabetes (T1D) who suffer from a substantially impaired awareness of hypoglycemia, its application is limited due to the lack of donors. Thus, pig-to-human islet xenotransplantation has been regarded as a promising alternative due to the unlimited number of "donor organs." Long-term xenogeneic islet graft survival in pig-to-non-human primate (NHP) models has mainly been achieved by administering the anti-CD154 mAb-based immunosuppressant regimen. Since the anti-CD154 mAb treatment has been associated with unexpected fatal thromboembolic complications in clinical trials, the establishment of a new immunosuppressant regimen that is able to be directly applied in clinical trials is an urgent need. We assessed an immunosuppressant regimen composed of clinically available agents at porcine islet transplantation in consecutive diabetic NHPs. Porcine islet graft survival in consecutive diabetic NHPs (n=7; >222, >200, 181, 89, 62, 55, and 34 days) without severe adverse events. We believe that our study could contribute greatly to the initiation of islet xenotransplantation clinical trials.