Long‐term control of diabetes in a nonhuman primate by two separate transplantations of porcine adult islets under immunosuppression

• Published in: American journal of transplantation Vol. 21; no. 11; pp. 3561 - 3572
• Main Authors: Kim, Jong‐Min, Hong, So‐Hee, Shin, Jun‐Seop, Min, Byoung‐Hoon, Kim, Hyun Je, Chung, Hyunwoo, Kim, Jiyeon, Bang, Yoon Ji, Seo, Sol, Hwang, Eung Soo, Kang, Hee‐Jung, Ha, Jongwon, Park, Chung‐Gyu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01.11.2021
• Subjects: Allografts; animal models: nonhuman primate; Animals; basic (laboratory) research/science; Cytomegalovirus; Diabetes; Diabetes Mellitus; endocrinology/diabetology; Globulins; Graft rejection; Immunoglobulins; Immunosuppression; Immunosuppression Therapy; Immunosuppressive agents; Induction therapy; Insulin; Interleukin 1 receptor antagonist; Intravenous administration; Islet cells; islet transplantation; Islets of Langerhans Transplantation; Macaca mulatta; Monkeys & apes; Monoclonal antibodies; Pancreas transplants; Pancreatic islet transplantation; Primates; Rapamycin; Swine; translational research/science; Transplantation, Heterologous; xenoantigen; Xenografts; xenotransplantation; translational research/science; islet transplantation; xenotransplantation; animal models: nonhuman primate; endocrinology/diabetology; xenoantigen; basic (laboratory) research/science
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.16704

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. An immunosuppression protocol of clinically applicable drugs achieves long‐term survival of two sequential porcine islet transplantation in nonhuman primates.