Affiliation:
1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul South Korea
2. Xenotransplantation Research Center Seoul National University College of Medicine Seoul South Korea
3. Animal Biotechnology Division, National Institute of Animal Science Rural Development Administration Wanju‐gun Jeonbuk‐do South Korea
Abstract
AbstractAims/IntroductionTo investigate the long‐term efficacy of various encapsulated xenogeneic islet transplantation, and to explore the impact of different donor porcine genetic traits on islet transplantation outcomes.Materials and MethodsDonor porcine islets were obtained from wild‐type, α1,3‐galactosyltransferase knockout (GTKO) and GTKO with overexpression of membrane cofactor protein genotype. Naked, alginate, alginate‐chitosan (AC), alginate‐perfluorodecalin (A‐PFD) and AC‐perfluorodecalin (AC‐PFD) encapsulated porcine islets were transplanted into diabetic mice.ResultsIn vitro assessments showed no differences in the viability and function of islets across encapsulation types and donor porcine islet genotypes. Xenogeneic encapsulated islet transplantation with AC‐PFD capsules showed the most favorable long‐term outcomes, maintaining normal blood glucose levels for 180 days. A‐PFD capsules showed comparable results to AC‐PFD capsules, followed by AC capsules and alginate capsules. Conversely, blood glucose levels in naked islet transplantation increased to >300 mg/dL within a week after transplantation. Naked islet transplantation outcomes showed no improvement based on donor islet genotype. However, alginate or AC capsules showed delayed increases in blood glucose levels for GTKO and GTKO with overexpression of membrane cofactor protein porcine islets compared with wild‐type porcine islets.ConclusionThe AC‐PFD capsule, designed to ameliorate both hypoxia and inflammation, showed the highest long‐term efficacy in xenogeneic islet transplantation. Genetic modifications of porcine islets with GTKO or GTKO with overexpression of membrane cofactor protein did not influence naked islet transplantation outcomes, but did delay graft failure when encapsulated.