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

Xenotransplantation. 2021 Mar;28(2):e12659. doi: 10.1111/xen.12659. Epub 2020 Nov 6.

Abstract

Background: 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.

Methods: We assessed an immunosuppressant regimen composed of clinically available agents at porcine islet transplantation in consecutive diabetic NHPs.

Results: Porcine islet graft survival in consecutive diabetic NHPs (n = 7; >222, >200, 181, 89, 62, 55, and 34 days) without severe adverse events.

Conclusion: We believe that our study could contribute greatly to the initiation of islet xenotransplantation clinical trials.

Keywords: clinically available immunosuppressants; diabetes mellitus; non-human primate; porcine islet transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 1* / surgery
  • Graft Rejection / prevention & control
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Islets of Langerhans Transplantation*
  • Primates
  • Swine
  • Transplantation, Heterologous

Substances

  • Immunosuppressive Agents