FAST LIGAND FOR PROTECTION OF TRANSPLANTED B ISLET CELLS

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DESCRIPTION: (Adapted from the Applicant's Abstract): The goal of the research proposed in this application is the bioengineering of allogeneic and xenogeneic beta islet cells that would be accepted for implantation without encapsulation in a manufactured biomaterial. Recent studies indicate that expression of Fas ligand (FasL) can induce tolerance by stimulation of apoptosis in Fas+ macrophages and activated T cells. Specific Aims of the Phase I research are as follows: (1) Determine if there is increased survival of islets from lpr mice in gld mice compared to gld into lpr mice. (2) Determine if beta islet cells from rat insulin promoter-FasL transgenic mice exhibit prolonged graft survival. (3) Determined if prolonged allograft survival will occur with grafts of mouse and human islets infected with FasL adenovirus. These studies are expected to provide the basis for Phase II work to develop transgenic pigs with human FasL under the control of the insulin promoter for beta islet cell transplantation. The commercial application would be the readily available supply of islet cells with stable Fas L expression for transplantation as an artificial pancreas in patients with diabetes mellitus. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE