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  • Title: A more persistent tolerance to islet allografts through bone marrow transplantation in minimal nonmyeloablative conditioning therapy.
    Author: Lee BW, Lee JI, Oh SH, Ahn YR, Chae HY, Lee MS, Lee MK, Kim KW.
    Journal: Transplant Proc; 2005 Jun; 37(5):2266-9. PubMed ID: 15964395.
    Abstract:
    INTRODUCTION: Islet transplantation is a therapeutic approach to prevent diabetes complications. However, the side effects of the required lifelong immunosuppressive regimens to prevent graft rejection restrict the impact of type 1 diabetes. One strategy to overcome these limitations is tolerance induction and graft acceptance through hematopoietic chimerism. In this study we investigated whether tolerance to major histocompatibility complex (MHC) and minor-disparate islet allografts could be induced by minimal nonmyeloablative conditioning and whether more persistent donor-specific islet allografts were accepted if the grafts were implanted with simultaneous bone marrow cells. METHODS: The donor and recipient mice were BALB/c(H-2(b)) and C57BL/6(H-2(d)), respectively. In group 1 streptozotocin-induced diabetic C57BL/6(H-2(d)) mice received only 500 islets of BALB/c(H-2(b)). Group 2 recipients conditioned with antilymphocyte serum, 100 cGy total body irradiation and cyclophosphamide were given islet cells of BALB/c(H-2(b)), but group 3 were simultaneously given 30 x 10(6) BALB/c(H-2(b)) mice BMCs and islet cells similar to group 2. RESULTS: We obtained 5% to 6% allogeneic donor chimerism and 60% graft survival at 80 days after islet transplantation in group 3. We observed lymphocyte infiltration around the islet without destruction of endocrine cells and the presence of strong insulin/glucagon-stained cells in group 3. CONCLUSION: This minimal nonmyeloablative conditioning therapy induced donor chimerism and immune tolerance between MHC- and minor-disparate (BALB/c-->C57BL/6) mice and long-term islet graft survival was obtained through cotransplantation of bone marrow cells.
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