The effect of fibroblast activation on vascularization in transplanted pancreatic islets

Background: Insufficient revascularization of transplanted pancreatic islets is an important reason why the long-term effects of pancreatic islet transplantation on type I diabetes patients have been so limited. The goal of this study was to investigate the role of fibroblasts (FBs) activated by tumor cell supernatants on the vascularization of transplanted pancreatic islets. Materials and methods: Pancreatic islets and activated or inactivated FBs were used for subrenal capsule transplantation. Mouse melanoma cell supernatants were used to activate FBs; the tests of the purity of the pancreatic islet cells of the donor, survival rate, and function of insulin secretion were performed to ensure high-quality transplants. Mice receiving the allogeneic transplantation were given tacrolimus and sirolimus to prevent rejection. The diabetic model was induced by streptozotocin. Results: Conditioned medium made of tumor cell supernatants was found to stimulate the expression of alpha-smooth muscle actin and vascular endothelial growth factor A to an extent notably greater than that of pancreatic islet transplantation alone or pancreatic islet transplantation combined with inactivated FBs. FBs from the recipient were associated with capillary density in the transplanted pancreatic islet most closely to that observed in isogenically transplanted pancreatic islets and the original pancreatic islet. In this way, activated FBs derived from the recipient combined with pancreatic transplantation were able to treat diabetes, and long-term survival was achieved. Conclusions: The current research sheds new light on the revascularization of transplanted pancreatic islets: activated FBs derived from the recipients, when transplanted alongside pancreatic tissue, can promote revascularization inside the transplanted pancreatic islet. (C) 2013 Elsevier Inc. All rights reserved.