The Applications of Bone Marrow-Derived Stem Cells to Induce Tolerance and Chimerism in Organ Transplantation

Abstract

Progress in understanding the cellular and molecular biology of the immune system, in the second half of the 20th century brings the transplantation of replacement organs and tissues in clinical reality to cure disease. Immunosuppressive agents that are part of nearly every transplantation procedure, are toxic to some extent and their chronic use predisposes the patient to the development of infection and cancer. Alternatives to immunosuppression include modulation of host immune system to reduce the immune response and the induction of a state of immunologic tolerance. Induction of hematopoietic mixed chimerism through donor bone marrow transplantation offers a promising approach for tolerance induction as a prelude to organ transplantation. Furthermore, mesenchymal stromal cells have important effects on the host immune system and possess immune modulation properties that make them attractive for potential use in organ transplantation as immunosuppressant. Both modalities might potentially provide novel therapeutic options for treatment/prevention of rejection and/or repair of organ allografts through their multifaceted properties. In this review, evidences for the tolerogenic properties and mechanisms of hematopoietic mixed chimerism as well as mesenchymal stromal cells effects on allograft surveillance are summarized.