Pre-Culture of Scaffolds with Vasculogenic Cells Improves Stem Cell-Derived β Cell Transplantation.

Abstract

Transplantation of stem cell-derived β cells is a promising treatment for type-1 diabetes, increasing the supply of insulin-producing cells beyond that of cadaveric islet transplantation. Transplant success is limited by cell death after transplantation, with insufficient oxygen and nutrient accessibility strongly contributing to apoptosis and de-differentiation. Herein, we investigate cotransplantation of endothelial cells and fibroblasts with stem cell-derived β cells to enhance survival and function posttransplantation. A microporous poly (lactide coglycolide) scaffold was used for culture and transplantation of stem cell-derived β cells. Coculture of the stem cell-derived β cells with endothelial cells and fibroblasts generated vascular networks during <i>in vitro</i> culture, which persisted through transplantation and enhanced <i>in vivo</i> vascularization. 7-days of <i>in vitro</i> culture supported enhanced survival of transplanted cells, though function in terms of insulin secretion and reduction of hyperglycemia was compromised. However, 3-days of preculture led to both improved survival and function of the stem cell-derived β cells, with transplant recipients demonstrating reduced fasting blood glucose levels. These studies demonstrate the potential and some constraints on the application of vascularization strategies to enhance function of stem cell-derived β cells with transplantation to extrahepatic sites.