ISLET ALLOGRAFT TOLERANCE & THYMIC TRANSPLANTATION OF STEM CELLS

这个项目的目的是在灵长类动物身上测试一种新的方法

The aim of this project is to test in primates a new method for producing tolerance to solid organ and tissue grafts implantation of donor CD34+ stem cells into the recipient thymus. These experiments test the validity and feasibility of this approach in a juvenile baboon model as a pre-clinical trial. In the islet transplant protocols, macaques were made diabetic by streptozocin induction. Then, Macaca nemestrina islets from tissue donors were used for pilot studies of islet transplantation into these diabetic recipients. In the baboon protocols, subfractions of stem cells are being tested as tolerogens in in vitro mixed lymphocyte assays to ascertain which subfraction will result in the least allostimulation. Thus, samples of baboon marrow are used for stem cell separations into various subfractions which are tested in vitro. Promising subfractions will be used in in vivo intrathymic injections to examine the effects of donor stem cells on 1) production and persis ten ce of microchimerism and 2) donor cardiac graft survival. Additional tissues are used for controls. FUNDING NIH grants RR00166, AI37747, and AI45487. Allen, M.D., Weyhrich, J., Akimoto, H., Gaur, L., Hall, J., Dalesandro, J., Sai, S., Thomas, R., Nelson, K.A., and Andrews, R.G. Prolonged allogeneic and xenogeneic microchimerism can be achieved in unmatched primates without immunosuppression by direct intrathymic implantation of CD34+ donor marrow cells. Cell. Immunol. 181:127-138, 1998. Allen, M.D., Gaur, L.K., Nelson, K., de Fries, R., Delio, P., Anasetti, C., and Andrews, R.G. Microchimerism is induced in unrelated primates without immunosuppression by immature CD34+ donor stem cells. Abstr. 10th Intl Congr. Immunol., New Delhi, India, November 1998.