Development of an Islet‐Stabilizing Implant Construct

Abstract

Islet transplantation for the purpose of treating type-1 diabetes is severely limited by several factors, including islet stability and viability. Following the isolation of islets from pancreas tissue, the ability of the islet to secrete physiologically relevant quantities of insulin is severely diminished; therefore, a current strategy for improving islet stability is to establish vascular perfusion to and within the islet, thus preserving islet function. The strategy used in this study was to create an islet implant construct that contains microvessel fragments which had been pre-cultured in a 3-dimensional collagen matrix. The islets were then placed between the microvessel gels, and the constructs were implanted into SCID mice. At 7 and 14 days post implantation, the constructs and surrounding tissues were removed, fixed, and prepared for histological analysis. Results from these experiments showed that the islets and some isolated cells expressed detectable quantities of insulin. Moreover, this insulin staining was associated with intact islets, but also with islets which were partially dissociated. Lastly, double cytochemical staining for insulin producing cells and endothelium indicate that insulin-producing islets contained endothelial cells, while islets devoid of endothelial cells did not stain for insulin. In conclusion, implant constructs containing islets and a pre-formed vasculature have been shown to stabilize islet function following 7 and 14 days of implantation.