Bone marrow-induced tolerance in the era of pancreas and islets transplantation

Enormous progress has been made in the field of solid organ adaptation recently because of the improvement in immunosuppression. Although powerful immunosuppressive drugs decrease the rate of acute rejection significantly, the long-term functional graft survival and tolerance induction remains poor. Chronic rejection is the main cause of graft failure. An electronic search was performed for articles on chimerism, tolerance, and immunologic perspectives of islet and pancreas transplantation along with referrals to our experience. Infusion of donor bone marrow-derived cells to create a chimeric state continue to be tested in clinical protocols intended to induce specific immunologic tolerance. The proposed mechanisms of immunologic engagement and the emergence of a tolerant state through mixed chimerism include central depletion of alloreactive cells, induction of T-cell anergy, and generation of suppressor cells by interactions between donor and host cells. In this setting, depletion of recipient T cells by different strategies and subsequent repopulation by donor hematopoietic cells after donor bone marrow infusion are prerequisites for tolerance induction. Many efforts have aimed to establish mixed chimerism along with tolerance in solid organ transplantation including pancreas and islets to facilitate engraftment. A review of the more important advances in the field and the future prospects combined with our experience to induce tolerance in the clinic and the laboratory is presented in this article.