Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival
Authors
Gao, QimengDavis, 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
UMass Chan Affiliations
MassBiologicsDocument Type
Journal ArticlePublication Date
2021-11-01
Metadata
Show full item recordAbstract
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.Source
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. 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.DOI
10.1111/xen.12713Permanent Link to this Item
http://hdl.handle.net/20.500.14038/51892PubMed ID
34951057Rights
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.ae974a485f413a2113503eed53cd6c53
10.1111/xen.12713