Addressing the challenge of autoimmunity in the treatmen of diabetes with stem cells

© 2013, Springer Science+Business Media New York 2013. All rights reserved. Type 1 diabetes mellitus is a complex autoimmune disease process encompassing a number of stages, the most significant of which is the loss of immunological tolerance and the initiation of immune dysfunction resulting in the selective destruction of pancreatic ß cells. Although exogenous insulin therapy has proven efficacious, it does not address the underlying cause of the disease. A treatment strategy encompassing immunosuppressive and ß cell replacement therapy that will promote immunological tolerance, without toxicity or the induction of lymphopenia is required for treatment of patients with hypoglycaemic unawareness. Importantly, this combination strategy must harness a therapy that provides a replacement source of insulin-producing ß cells without toxic side effects associated with long-term immunosuppression and induces tolerance to the replacement ß cells in order to prevent destruction by allo- and autoreactive T cells. Here, we discuss the current immunosuppressive therapies and potential sources of replacement ß cells and review the pitfalls in current combined immunosuppression and islet transplant therapy. Finally, we examine possible combination strategies including stem cells that are likely to succeed in fulfiling the above criteria for the treatment of diabetes in the future.