The ultimate goal is to treat human Type I (insulin-deficient) diabetes mellitus by transplantation of fetal pancreas tissue. The immediate goal is to establish, in a larger animal model (pigs), a safe, effective, and practical method for fetal pancreas transplantation which can be used for diabetic patients. We have already verified in pigs that fetal pancreas transplants can reverse diabetes. Developmental and immunological characteristics of fetal pancreas have been determined and the techniques and assay methods necessary to carry out the proposed studies have been established. Using already available knowledge and techniques, we will expand our research in the following areas: 1. Development of methods to circumvent rejection of pig fetal pancreas. a. Perfection of donor pancreas treatment for removal of passenger leukocytes, with special emphasis on treatment with immunotoxin. b. Determination of survival times of treated fetal pancreas in donor-recipient combinations with known incompatibilities. Pancreas will be transplanted without recipient immunosuppression. When this fails, with immunosuppression, especially by CSA. c. Specific immunotherapy for recipients by transfusion of donor type or pooled blood or by donor-type bone marrow cells in conjunction with a short course of immunosuppression, especially by CSA or ALS. 2. Reversal of experimental diabetes in pigs by transplantation of fetal pancreas using the method developed in the above studies and long-term monitoring of diabetes reversed recipients. 3. Protection of islet iso- and allografts against destruction by the autoimmune process present in diabetic Non-Obese Diabetic (NOD) mice. 4. Development of methods for maintenance and transportation of fetal pancreas prepared for transplantation. Methodologies developed from these studies should prevent fetal pancreas transplants from destruction by immune response to both allo- and islet antigens.
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