The longterm objective of this proposal is in vitro production of insulin-secreting human B-cells in sufficient quantities to reverse diabetes in human patients after transplantation of cell masses or neoformed islets. The immediate aims outlined in this proposal are increases in neonatal rat B-cell production by supplementation of the culture medium with hormones and growth factors as well as by altering the substratum. B-cell proliferation and insulin secretory activity will be monitored by cell counting, radioimmunoassay, histology, electron microscopy, and immunocytochemistry. In vivo survival and function of cultured rat B-cells and islets will be tested in animals. Cultured B-cells and islets will be transplanted beneath the kidney capsule in experimental rats in the absence of immunosuppression. Treatments such as prolonged culture, high oxygen tension, or cloning of B-cells will greatly reduce, inactivate or eliminate rejection-initiating cells in the cultures. Graft viability will be assessed histologically in normal rats as well as functionally in streptozotocin-diabetic rats. Function of cultured B-cells and islets is monitored by reversal of diabetes. We anticipate to apply to fetal human B-cell cultures the methods learned from the rat model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038144-03
Application #
3237370
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-09-01
Project End
1992-08-31
Budget Start
1990-09-01
Budget End
1992-08-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Kansas
Department
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160