Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival
Kirk, Allan D
UMass Chan AffiliationsMassBiologics
Document TypeJournal Article
MetadataShow full item record
AbstractPorcine 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.
SourceGao 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. Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival. Xenotransplantation. 2021 Nov;28(6):e12713. doi: 10.1111/xen.12713. Erratum in: Xenotransplantation. 2022 Mar 11;:e12741. PMID: 34951057; PMCID: PMC8715890.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/51892
Rights© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.