The publication of the promising results of the Edmonton protocol in 2000 generated optimism for islet transplantation as a potential cure for Type 1 Diabetes Mellitus. Unfortunately, follow-up data revealed that less than 10% of patients achieved long-term insulin independence. More recent data from other large trials like the Collaborative Islet Transplant Registry show incremental improvement with 44% of islet transplant recipients maintaining insulin independence at three years of follow-up. Multiple underlying issues have been identified that contribute to islet graft failure, and newer research has attempted to address these problems. Stem cells have been utilized not only as a functional replacement for β cells, but also as companion or supportive cells to address a variety of different obstacles that prevent ideal graft viability and function. In this paper, we outline the manners in which stem cells have been applied to address barriers to the achievement of long-term insulin independence following islet transplantation. 1. Introduction: An Emerging Field in Treatment for Type I Diabetes Mellitus The promising results of the Edmonton protocol, published in 2000, brought new enthusiasm to the field of islet transplantation. With this method, Shapiro et al. combined a glucocorticoid-free immunosuppression regimen with improved techniques for islet isolation and purification, followed by transplantation via percutaneous transhepatic portal embolization of 4000 islet equivalents per kilogram of body weight. Although most patients required repeated transplants to achieve insulin independence, at a median follow-up of 11.9 months, all seven patients who had undergone islet transplantation had no requirements for exogenous insulin. Prior to the procedure, recipients uniformly suffered from recurrent severe hypoglycemic episodes, and they experienced resolution of these episodes with increased stability in blood glucose values afterwards. No major complications occurred. These outcomes generated hope that islet transplantation would optimize metabolic control in patients with Type 1 Diabetes Mellitus (T1DM) and obviate the need for exogenous insulin administration [1]. However, to the great disappointment of the medical and research communities, long-term follow-up of transplanted patients revealed less encouraging outcomes. Among a cohort of 65 patients followed for an average of 35.5 months after transplantation, most were able to achieve short-term insulin independence, but 92.5% eventually required insulin to maintain glycemic control. These
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