Advances in Islet Transplantation Including Development of a Novel Cell Encapsulation Platform for the Treatment of Diabetic Pets

Abstract

Islet transplantation as a treatment for type-1 diabetes in humans has reached a plateau, and major breakthroughs in stem-cell based therapies and immunoprotection strategies are now needed to advance the field. The primary goal within this dissertation was to approach innovation in islet transplantation from a new perspective: veterinary medicine and canine diabetes. Canine diabetes, while strikingly similar to type-1 diabetes in humans, has been entirely overlooked as a market for islet transplantation, and is in significant need of better treatment options. The obvious clinical need and regulatory advantage in veterinary medicine creates an attractive environment to cultivate much needed innovation in the field of islet transplantation. This overall goal was addressed with the following specific aims: 1] develop and optimize practical, ethical, and cost effective methods for obtaining transplant quality islets from canine donors 2] demonstrate and evaluate long-term efficacy of an alternative (non-alginate) hydrogel for immunoprotected islet transplantation in an allogeneic diabetic rat model 3] develop a non-toxic, simple, and readily translatable method for fabricating hydrogel (non-alginate) microspheres for cell encapsulation and delivery In accomplishing these aims, significant groundwork for islet transplantation as a treatment option for diabetic canines has been laid. A major focus of this research was in the evaluation and development of an islet encapsulation system based on a hyaluronic acid (HA) based hydrogel as an alternative to standard alginate microspheres. Islets transplanted within the HA gel reversed diabetes in immune competent allogeneic rats for a minimum of 10 months. In light of these results, I developed, characterized, and patented a novel method for producing islet-laden HA hydrogel microspheres designed for use with readily available materials and cGMP complaint equipment. Furthermore, this novel method has great potential as a platform technology for generating cell-laden hydrogel microspheres using a variety of biomaterials for broad application in regenerative medicine and three-dimensional tissue culture.