The effect of bone marrow transplantation on survival of allogeneic pancreatic islets with short-term tacrolimus conditioning in rats.

OBJECTIVE: Specific immune tolerance achieved by induction of lymphocyte chimerism could reduce the need for immunosuppressive therapy in pancreatic islet transplantation. The aim of the experiment was to assess the effect of pre-treatment with donor specific bone marrow on the function of allogeneic islets under the conditions of a short-term immunosuppression. METHODS: Male Lewis-Brown Norway and female Brown Norway rats were used as donors and recipients, respectively. In all recipients diabetes was induced by streptozotocin. In Group 1, 5 animals were treated only by islet transplantation. In Group 2, 7 rats underwent islet transplantation after previous 45-day therapy with tacrolimus 1 mg/kg and hydrocortisone 2 mg/kg, which was stopped 6 days after islet transplantation. Recipients in Group 3 (n = 16) were treated as Group 2 (n = 7) and, in addition, underwent transplantation of 10(8) bone marrow cells 10 days after initiation of immunosuppressive therapy. RESULTS: In Group 1, islets were rejected after a median survival time of 11 days. In Groups 2 and 3, islet function has been demonstrated for more than 70 days in all animals. CONCLUSIONS: Short-term immunosuppressive therapy prevented islet rejection for at least 70 days. Longer follow-up period is needed to show whether peripheral microchimerism induced by bone marrow transplantation will further improve islet survival in non-immunosuppressed recipients.