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

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

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1 Scopus citations

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.

Original languageEnglish
Pages (from-to)3561-3572
Number of pages12
JournalAmerican Journal of Transplantation
Volume21
Issue number11
DOIs
StatePublished - Nov 2021

Bibliographical note

Funding Information:
This work was supported by a grant from the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry for Health and Welfare, Republic of Korea (Grant No. HI13C0954). This work was partly supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIT) (Grant No. NRF‐2020R1A2C1004557, NRF‐2019R1A2C2085287 to Kim JM and Park CG, respectively). The authors would like to thank S. K. Park, J. W. Choi, and M. S. Lee for isolating the porcine islets; H. Y. Nam for conducting FACS; W. Y. Jung, M. S. Kim, G. E. Lee, J. E. Kim and S.E. Kwon for caring for all of the NHPs.

Publisher Copyright:
© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons

Keywords

  • animal models: nonhuman primate
  • basic (laboratory) research/science
  • endocrinology/diabetology
  • islet transplantation
  • translational research/science
  • xenoantigen
  • xenotransplantation

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