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 marrow hematopoietic stem cell (HSC) itself rather than its derivatives. HSC chimerism achieved through bone marrow transplantation (BMT) may affect type I diabetes in two ways: first, to induce tolerance to pancreas and islet cell 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 type I diabetes has reversed the systemic diabetic autoimmune process. Donor HSCs can also be utilized for the induction of donor-specific tolerance to islet cell transplants. Islet or whole pancreas transplantation is the most physiologic approach to treating type I diabetes. Currently, this is limited by the requirement for high-dose chronic nonspecific immunosuppression to prevent rejection. Despite these agents, chronic rejection remains the primary cause for late graft loss. Donor-specific tolerance eliminates the requirement for immunosuppression and prevents the development of chronic rejection. Bone marrow transplantation does have limitations. In particular these limitations include the morbidity associated with lethal conditioning, graft-versus-host disease, and failure of engraftment. Currently the morbidity and mortality associated with lethal conditioning could not be justified for 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 HSC chimerism affecting diabetes.
Domenick
M A
MA
Department of Surgery, Medical College of Pennsylvania, Hahnemann University, Broad and Vine Streets, Philadelphia, Pennsylvania 19102, USA.
Ildstad
S T
ST
D000818:Animals; D015551:Autoimmunity; D016026:Bone Marrow Transplantation / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology* / Q000601:surgery*; D006084:Graft Rejection / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009030:Mosaicism; D019172:Transplantation Conditioning; D023001:Transplantation Tolerance