Application of an Endothelialized Modular Construct for Islet Transplantation in Syngeneic and Allogeneic Immunosuppressed Rat Models

Abstract

Modular tissue engineering is a novel approach to assemble tissues with an inherent vascularization. In this article, we evaluated whether endothelialized module-driven vascularization enhances islet engraftment in diabetic rats. Two thousand islets were transplanted in the omental pouch of syngeneic and allogeneic immunosuppressed diabetic recipients as free islets, islets in collagen modules, or islets in endothelialized modules. Transplantation of islets in endothelialized modules significantly increased the vessel density compared with controls. Donor green fluorescent protein-positive endothelial cells (ECs) formed vessels in proximity to transplanted islets; donor vessels connected to host vasculature as the vessels included erythrocytes in their lumens and were supported by host smooth muscle cells by 21 days. Transplantation of 2000 islets reversed diabetes in two of five of syngeneic recipients until 60 days, although there was no apparent benefit to islet function of adding ECs relative to collagen modules without EC. However, there was a trend toward increased viability when islets were implanted in endothelialized modules compared with collagen modules at 21 days. Meanwhile, 2000 islets in allogeneic immunosuppressed recipients lowered blood glucose levels short term, but there was graft failure within 1 week. This study explored the simultaneous transplantation of primary ECs with islets in diabetic recipients. The endothelialized modular approach increased vessel density around transplanted islets. Further modulation (i.e., acceleration) of vessel maturation, is presumed necessary to improve islet engraftment.