Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival

Gao Qimeng, Davis Robert, Fitch Zachary, Mulvihill Michael, Ezekian Brian, Schroder Paul, Schmitz Robin, Song Mingqing, Leopardi Frank, Ribeiro Marianna, Miller Allison, Moris Dimitrios, Shaw Brian, Samy Kannan, Reimann Keith, Williams Kyha, Collins Bradley, Kirk Allan D.

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Porcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of a clinically available immunosuppressive regimen. We tested two clinically relevant induction agents in a non-human primate (NHP) islet xenotransplantation model to compare depletional versus nondepletional induction immunosuppression. Neonatal porcine islets were isolated from GKO or hCD46/GKO transgenic piglets and transplanted via portal vein infusion in diabetic rhesus macaques. Induction therapy consisted of either basiliximab (n = 6) or rhesus-specific anti-thymocyte globulin (rhATG, n = 6), combined with a maintenance regimen using B7 costimulation blockade, tacrolimus with a delayed transition to sirolimus, and mycophenolate mofetil. Xenografts were monitored by blood glucose levels and porcine C-peptide measurements. Of the six receiving basiliximab induction, engraftment was achieved in 4 with median graft survival of 14 days. All six receiving rhATG induction engrafted with significantly longer xenograft survival at 40.5 days (P = 0.03). These data suggest that depletional induction provides superior xenograft survival to nondepletional induction, in the setting of a costimulation blockade-based maintenance regimen.

Original languageEnglish (US)
Article numbere12713
JournalXenotransplantation
Volume28
Issue number6
DOIs
StatePublished - Nov 1 2021
Externally publishedYes

Bibliographical note

Funding Information:
This study was funded by National Institutes of Health (NIH) grant U01‐ AI090956 (A.D.K.). We would like to thank the Duke University Substrate Core for their assistance in serum rhesus CMV level monitoring. Anti–rhesus thymocyte globulin used in this study was produced by the NIH Nonhuman Primate Reagent Resource (National Institute of Allergy and Infectious Diseases contract HHSN 2722001300031C).

Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • belatacept
  • islet transplantation
  • rhesus anti-thymocyte globulin
  • xenotransplantation

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