Extrahepatic islet transplantation with microporous polymer scaffolds in syngeneic mouse and allogeneic porcine models.

Abstract

Intraportal transplantation of islets has successfully treated select patients with type 1 diabetes. However, intravascular infusion and the intrahepatic site contribute to significant early and late islet loss, yet a clinical alternative has remained elusive. We investigated non-encapsulating, porous, biodegradable polymer scaffolds as a vehicle for islet transplantation into extrahepatic sites, using syngeneic mouse and allogeneic porcine models. Scaffold architecture was modified to enhance cell infiltration leading to revascularization of the islets with minimal inflammatory response. In the diabetic mouse model, 125 islets seeded on scaffolds implanted into the epididymal fat pad restored normoglycemia within an average of 1.95 days and transplantation of only 75 islets required 12.1 days. Increasing the pore size to increase islet-islet interactions did not significantly impact islet function. The porcine model was used to investigate early islet engraftment. Increasing the islet seeding density led to a greater mass of engrafted islets, though the efficiency of islet survival decreased. Transplantation into the porcine omentum provided greater islet engraftment than the gastric submucosa. These results demonstrate scaffolds support murine islet transplantation with high efficiency, and feasibility studies in large animals support continued pre-clinical studies with scaffolds as a platform to control the transplant microenvironment.