This proposal represents a continuation of our research in the area of islet cell culture and transplantation. The work is intended to serve as a basis for the eventual application of islet cell transplantation in Type 1 diabetes. Experiments involve the investigation of a unique method for the production of non- immunogenic islets which can be transplanted without immunosuppression between animals disparate at the major histocompatibility locus. Further understanding of the mechanism by which altered immunogenicity is attained is pursued. Chemically induced forms of Type 1 diabetes and an experimental model of spontaneous Type 1 diabetes are being examined to assess the utility of the technologies developed in the reversal of these hyper-glycemic-insulinopenic syndromes. The central question concerns the effectiveness of genetically mismatched (allogeneic but not immunogenic) islet grafts in the prevention of recurrence of autoimmune diabetes. The approach centers on the acquisition of morphological data, coupled with bio-chemical and physiological studies. Techniques of immunoassay, morphometric analysis at the light microscopical level, immunocytochemistry, spectrophotometry, chromatography, enzymology, tissue culture, transplantation permit the correlation of morphological, biochemical and physiological parameters. Major questions remain as barriers to human islet cell transplantation. Efficient methods must be developed for the isolation and purification of human islets. Can methods be developed permitting the purification of islet endocrine grafts circumventing rejection without the need for patient immunosuppression? Will the etiology of human Type 1 diabetes be re-expressed in the transplanted islet grafts, compromising its function? Are there other factors within the recipient's environment that pose a threat to the established allograft? It is hoped that experiments in this proposal will provide basic research which may lead to the answers to some of these questions.
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