Long-term control of diabetes in a nonhuman primate by two separate transplantations of porcine adult islets under immunosuppression
- PMID: 34058060
- DOI: 10.1111/ajt.16704
Long-term control of diabetes in a nonhuman primate by two separate transplantations of porcine adult islets under immunosuppression
Abstract
Porcine islet transplantation is an alternative to allo-islet transplantation. Retransplantation of islets is a routine clinical practice in islet allotransplantation in immunosuppressed recipients and will most likely be required in islet xenotransplantation in immunosuppressed recipients. We examined whether a second infusion of porcine islets could restore normoglycemia and further evaluated the efficacy of a clinically available immunosuppression regimen including anti-thymocyte globulin for induction; belimumab, sirolimus, and tofacitinib for maintenance and adalimumab, anakinra, IVIg, and tocilizumab for inflammation control in a pig to nonhuman primate transplantation setting. Of note, all nonhuman primates were normoglycemic after the retransplantation of porcine islets without induction therapy. Graft survival was >100 days for all 3 recipients, and 1 of the 3 monkeys showed insulin independence for >237 days. Serious lymphodepletion was not observed, and rhesus cytomegalovirus reactivation was controlled without any serious adverse effects throughout the observation period in all recipients. These results support the clinical applicability of additional infusions of porcine islets. The maintenance immunosuppression regimen we used could protect the reinfused islets from acute rejection.
Keywords: animal models: nonhuman primate; basic (laboratory) research/science; endocrinology/diabetology; islet transplantation; translational research/science; xenoantigen; xenotransplantation.
© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.
References
REFERENCES
-
- Hering BJ, Clarke WR, Bridges ND, et al. Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 2016;39(7):1230-1240.
-
- Liu Z, Hu W, He T, et al. Pig-to-primate islet xenotransplantation: past, present, and future. Cell Transplant. 2017;26(6):925-947.
-
- Samy KP, Martin BM, Turgeon NA, Kirk AD. Islet cell xenotransplantation: a serious look toward the clinic. Xenotransplantation. 2014;21(3):221-229.
-
- Shin JS, Kim JM, Kim JS, et al. Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets. Am J Transplant. 2015;15(11):2837-2850.
-
- Shin J-S, Kim J-M, Min B-H, et al. Pre-clinical results in pig-to-non-human primate islet xenotransplantation using anti-CD40 antibody (2C10R4)-based immunosuppression. Xenotransplantation. 2018;25(1):e12356.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Medical