The 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 from adult rodent sources. These islets can be transplanted without any form of immunosuppression across major histocompatibility barriers. Further understanding of the mechanism by which altered immunogenicity is attained will be pursued. Methods of selective cell culture in which cells necessary for immune recognition can be controlled in vitro will also be explored. In addition, experimental animal models of human Type 1 diabetes of both immunological as well as chemical etiology will be examined to assess the utility of the technologies developed in the reversal of these hyperglycemic-insulinopenic syndromes. The approach centers on the acquisition of morphological data, coupled with biochemical and physiological studies. Techniques of immunoassay, morphometric analysis at the ultrastructural and light microscopical levels, immunocytochemistry, spectrophotometry, chromatography, enzymology, tissue culture, transplantation, and tissue culture permit the correlation of morphological, biochemical and physiological parameters. Major questions remain as barriers to human islet cell transplantation. Can efficient methods 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 Type 1 diabetes be reexpressed in the transplanted grafts thus compromising their function? If so, does the reexpression of the syndrome relate to the immunological similarity between host and donor - can mismatching (allografts) circumvent the autoimmune phenomenon. It is hoped that experiments outlined in this proposal will provide basic research which may lead to the answers to some of these questions.
