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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK020827-10
Application #
3226815
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1977-09-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
10
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kenmochi, T; Miyamoto, M; Une, S et al. (2000) Improved quality and yield of islets isolated from human pancreata using a two-step digestion method. Pancreas 20:184-90
Kenmochi, T; Miyamoto, M; Sasaki, H et al. (1998) LAP-1 cold preservation solution for isolation of high-quality human pancreatic islets. Pancreas 17:367-77
Hober, C; Benhamou, P Y; Watt, P C et al. (1997) A new culture method for human pancreatic islets using a biopore membrane insert. Pancreas 14:199-204
Mullen, Y; Arita, S; Kenmochi, T et al. (1997) A two-step digestion process and LAP-I cold preservation solution for human islet isolation. Ann Transplant 2:40-5
Kenmochi, T; Miyamoto, M; Mullen, Y (1996) Protection of mouse islet isografts from nonspecific inflammatory damage by recipient treatment with nicotinamide and 15-deoxyspergualin. Cell Transplant 5:41-7
Benhamou, P Y; Kenmochi, T; Miyamoto, M et al. (1995) Fetal pancreas transplantation in miniature swine. V. The functional and immunodulatory effects of ultraviolet light on fetal pig islets. Transplantation 59:1660-5
Yi, O; Stein, E; Mullen, Y (1995) Abrogation of allospecific T lymphocyte responses in swine by ultraviolet light-B irradiation. Immunobiology 192:353-64
Une, S; Kenmochi, T; Miyamoto, M et al. (1995) Induction of donor-specific unresponsiveness in NIH minipigs following intrathymic islet transplantation. Transplant Proc 27:142-4
Kenmochi, T; Une, S; Miyamoto, M et al. (1995) Successful intrathymic allografts of porcine pancreatic islets without continuous immunosuppression. Transplant Proc 27:145-7
Kenmochi, T; Mullen, Y; Miyamoto, M et al. (1994) Protection of mouse islet isografts from early transplantation damage by nicotinamide treatment of recipients. Transplant Proc 26:693

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