Engineering Issues in Cell Based Insulin Replacement Therapies
Klearchos K. Papas, Surgery, Diabetes Institute for Immunology and Transplantation, University of Minnesota, MMC 195, 420 Delaware Street SE, Minneapolis, MN 55455
The prevention, treatment, and cure of type 1 diabetes (T1D) is an international health priority. Current diabetes management with insulin therapy does not provide the tight physiological minute to minute regulation of blood glucose leading to devastating life-threatening complications that include stroke, cardiac infarction, blindness, neuropathy and chronic renal failure. Vascularized pancreas transplantation is currently the only available option that enables physiological blood glucose control in patients with severe uncontrolled diabetes, but requires major surgery and potent immunosupression. Islet transplantation is an attractive alternative to vascularized pancreas transplantation since it may restore normoglycemia through a minor surgical procedure with minimal immuno¬suppression. The feasibility and efficacy of islet transplantation was recently established with the landmark “Edmonton protocol” and subsequent clinical trials that demonstrated that human islet allografts can consistently result in insulin independence with excellent metabolic control when glucocorticoid-free immunosuppression is combined with the infusion of an adequate islet mass. There are, however, major challenges that remain prior to larger scale, cost-effective application of islet transplantation. These relate to the limited human islet supply from cadavers, poor islet quality due to donor brain death, long-cold ischemia times during organ procurement, storage, transport as well as stresses associated with current islet processing protocols, as well as requirements for potent immunosuppression. Improvement of human pancreas procurement and preservation protocols as well as islet processing and transplantation techniques are areas of research actively pursued in a number of labs around the world, and can have a substantial and immediate impact in the field. However, the next major breakthrough will be associated with the demonstration of consistent diabetes reversal in the pre-clinical and clinical setting following transplantation of islets obtained from a renewable source that provides an unlimited supply, and restores normoglycemia with minimal or no immunosuppression. This breakthrough will require major advancements that can only be accomplished with close collaboration between scientists from multiple disciplines that include medicine, molecular and cellular biology, immunobiology as well as engineering. In this presentation we provide an overview of the past, the present as well as a vision of the future of islet transplantation and the contributions of engineering towards the treatment of T1D worldwide.