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

Jong Min Kim, So Hee Hong, Hyunwoo Chung, Jun Seop Shin, Byoung Hoon Min, Hyun Je Kim, Jiyeon Kim, Eung Soo Hwang, Hee Jung Kang, Jongwon Ha, Chung Gyu Park

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Article numbere12659
JournalXenotransplantation
Volume28
Issue number2
DOIs
StatePublished - 1 Mar 2021

Keywords

  • clinically available immunosuppressants
  • diabetes mellitus
  • non-human primate
  • porcine islet transplantation

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