Selective local irradiation improves islet engraftment and survival in intra–bone marrow islet transplantation

Abstract

BackgroundBone marrow (BM) is as an alternative site for islet transplantation, but it is not an immunoprotected microenvironment and allogeneic islets are rejected. However, the BM, for its structure and anatomic position, offers the possibility to modulate microenvironment by local interventions. We here investigate whether local irradiation is able to improve islet engraftment and prevent rejection in BM in the absence of immunosuppression. MethodsA model of BM local irradiation was set up. Islets were transplanted in syngeneic and fully major histocompatibility complex–mismatched recipients in control and locally irradiated BM; gain of normoglycemia and time to rejection were evaluated. ResultsBM local irradiation proved to be a selective and safe procedure. Syngeneic islet transplantation into locally irradiated BM had better outcome compared with not irradiated recipients in terms of capacity to gain normoglycemia (100% versus 56% in irradiated versus not irradiated mice). In the allogenic setting, glycemia was significantly lower in the first days after transplantation in the group of irradiated mice and local irradiation also delayed time to graft rejection (from 4 ± 1 days for not irradiated to 11 ± 1 days for locally irradiated mice). DiscussionThese data indicate that local immunosuppression by irradiation before islet transplantation in BM favors islet engraftment and delays time to rejection.