Diabetes mellitus (Type 1) affects over 100 million individuals worldwide and approximately 1.5 million in the U.S. This disease results in direct medical and indirect non-medical costs (e.g., disability, premature mortality) of as much as 10 billion dollars annually. Clinical trials of human islet transplantation have demonstrated the feasibility of reversing diabetes. However, two major problems (immunorejection and an insufficient quantity of islets) have limited its use as a standard treatment. Primary xenograft tissue (e.g., from pigs) offers the potential to overcome the shortage of transplantable tissue, but presents additional risks, such as the transmission of zoonotic disease. Another approach involves the in vitro expansion of islets in culture. The investigators have recently shown that co-culture of islets with a novel biomaterial derived from the small intestinal submucosa (SIS): (1) increases islet mass, (2)increases islet insulin response to glucose, (3)increases the islet insulin content, and (4)induces proliferating cell nuclear-antigen on islet cells. Collectively, these data suggest that one or more components in SIS cause islet, specifically Beta cell, proliferation in vitro. The phase I stage of this project found that extracted, but not solubilized SIS elicited islet proliferation. During Phase I, the investigators were able to refine processing methods to extract SIS to allow a standardized preparation with islet proliferating activity. In this Phase II application the investigators propose to use this information gained in Phase I to develop two novel products: (1) an SIS based tissue culture media for in vitro proliferation of islets, and (2) a composite biomaterial of SIS-islets which can be transplanted as either a dermal graft (especially for the treatment of diabetic ulcers) or a vascular graft (for systemic treatment.) The investigators have support from Cook Biotech, Inc. who will serve as their Phase III partner for both of these products. These products will have importance in enhancing islet transplantation as a treatment and/or cure for type I diabetes.
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| Woods, E J; Walsh, C M; Sidner, R A et al. (2004) Enhanced recovery of cryopreserved islets using SIS. Transplant Proc 36:1139-42 |
| Woods, E J; Walsh, C M; Sidner, R A et al. (2004) Improved in vitro function of islets using small intestinal submucosa. Transplant Proc 36:1175-7 |
