Pancreatic Islet Transplantation in Extrahepatic Sites: Evaluation of the Venous Sac in Large Mammal Models

Background: The long-term clinical efficacy of intraportal islet transplantation is hampered by islet loss due to inflammation, oxidative stress, and insufficient vascularization. This study explores the venous sac as an alternative implantation site for islet transplantation in large animal models.Methods: An immunosuppressed, diabetic cynomolgus monkey received allogeneic islet implants in its mesenteric venous sac, with metabolic assessments over 112 days. Dogs underwent islet autotransplantation into various venous sacs, with their glycemic control and other metabolic parameters monitored for 1 month.Results: In a nonhuman primate, the mesenteric venous sac site improved glycemic control over a 3-month period, followed by destabilization of graft function. Histological studies revealed healthy islets. The lack of mononuclear cell infiltrate suggested no signs of graft rejection. Saphenous venous sacs in dogs showed superior glycemic control, reduced insulin requirements, and maintained C-peptide levels, comparable to intraportal transplantation. Histological analyses confirmed islet preservation and graft vascularization in saphenous venous sacs.Conclusion: This study provides preclinical evidence in support of the venous sac as a valuable extrahepatic location for pancreatic islet implantation. We found that the saphenous vein is a more effective site for islet engraftment than the mesenteric vein. This study offers potential benefits for improving the success rates of clinical islet transplantation.