Autologous Hematopoietic Stem Cell Transplantation for Tolerance Induction in a Mouse Model of Solid Organ Transplantation

The need for long term immunosuppression negatively impacts long term survival and quality of life for solid organ transplant patients. One solution for this would be establishment of immune tolerance. Autologous HSCT has been used clinically for the restoration of self-tolerance in autoimmune disease. We tested whether autologous HSCT and a short treatment with rapamycin could result in tolerance to fully MHC-mismatched allografts. Mice that received HSCT and a short course of the mTORi rapamycin demonstrated significantly prolonged allograft survival compared to untreated and rapamycin-only treated controls. Immunologic studies showed that HSCT-treated mice displayed active immune regulation as demonstrated by a primary MLR response, markedly diminished donor specific antibody levels and significantly higher frequencies of CD4+CD25+FOXP3+ Tregs. These data provide a rationale for human clinical trials to examine the ability of autologous stem cell transplantation to induce tolerance in liver transplant patients (ASCOTT) which are now ongoing.M.Sc