Impact of bone marrow transplantation on type I diabetes

Type I diabetes is a systemic autoimmune disease. Evidence is accumulating that autoimmune diseases such as type I diabetes are linked to the bone mar row hematopoietic stem cell (HSC) itself rather than its derivatives, HSC c himerism achieved through bone marrow transplantation (BMT) may affect type I diabetes in two ways: first, to induce tolerance to pancreas and islet c ell transplants; and second, to reverse the autoimmune process prior to the development of terminal complications. Transplantation of bone marrow from normal donors into patients with hematologic malignancy and coexistent typ e I diabetes has reversed the systemic diabetic autoimmune process. Donor H SCs can also be utilized for the induction of donor-specific tolerance to i slet cell transplants. Islet or whole pancreas transplantation is the most physiologic approach to treating type I diabetes, Currently, this is limite d by the requirement for high-dose chronic nonspecific immunosuppression to prevent rejection. Despite these agents, chronic rejection remains the pri mary cause for late graft loss. Donor-specific tolerance eliminates the req uirement for immunosuppression and prevents the development of chronic reje ction, Bone marrow transplantation does have limitations. In particular the se limitations include the morbidity associated with lethal conditioning, g raft-versus-host disease, and failure of Engraftment. Currently the morbidi ty and mortality associated with lethal conditioning could no; be justified fo; tolerance induction or interruption of the autoimmune state in type I diabetes. The goal of current research is to identify those factors in both recipient and donor that optimize engraftment to reverse the risk/benefit ratio associated with BMT. This article reviews the state of the art for HS C chimerism affecting diabetes.