Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gao, Q; Davis, R; Fitch, Z; Mulvihill, M; Ezekian, B; Schroder, P; Schmitz, R; Song, M; Leopardi, F; Ribeiro, M; Miller, A; Moris, D; Shaw, B; Samy, K; Reimann, K; Williams, K; Collins, B; Kirk, AD

Published Date

  • November 2021

Published In

Volume / Issue

  • 28 / 6

Start / End Page

  • e12713 -

PubMed ID

  • 34951057

Pubmed Central ID

  • PMC8715890

Electronic International Standard Serial Number (EISSN)

  • 1399-3089

Digital Object Identifier (DOI)

  • 10.1111/xen.12713

Language

  • eng

Conference Location

  • Denmark