Transplantation tolerance through mixed chimerism

The major factors that limit the success of organ transplantation are the host immune response to the foreign graft and the adverse effects of the chronic immunosuppressive therapy required to suppress this immune response. Deliberately establishing tolerance towards the donor tissue by reprogramming the immune system of the recipient thus holds great promise in improving organ transplant survival and eliminating the untoward effects of chronic drug therapy. The transplantation of donor bone marrow into recipients who are appropriately conditioned to allow development of either full or mixed chimerism has long been recognized to effectively induce donor-specific tolerance. Despite the demonstrated effectiveness of this technique, use of the mixed chimerism strategy in regular clinical practice has been hampered by the toxic side effects inherent to conventional bone marrow transplantation protocols. This Review addresses recent advances in preclinical and clinical studies inducing transplantation tolerance through mixed chimerism and discusses both the potential and the challenges of this approach.