Immunoregulatory properties of bone marrow stem cells and their potential use in solid organ transplantation

Abstract

Background: Long-term results of organ transplantation remain rather unsatisfactory, mainly because of chronic rejection and complications associated with side effects of immunosuppressive therapy. Induction of specific immunotolerance to donor alloantigens would greatly diminish or prevent these problems. Conclusons: Tolerance to allograft has been successfully induced in laboratory animals by first transplanting bone marrow hematopoietic stem cells from the prospective organ donor into the recipient, thereby creating a mixed chimera in which donor’s and recipient’s hematopoieses coexist and tolerate each other. However, so far, the results of attempts to extend such studies from laboratory animals to humans have not been very successful. In the present article we review different mechanisms involved in the onset of immune tolerance as well as the immunoregulatory potential of bone-marrow-derived stem cells transplanted simultaneously with the organ graft (kidney). We also elucidate key problems related to the induction of tolerance in humans and describe the first encouraging experimental results in humans simultaneously receiving renal and hematopoietic stem cell grafts.