Mesenchymale Stammzellen vermitteln die Akzeptanz solider Organtransplantate durch Indolamin 2,3-Dioxygenase

Abstract

The induction of tolerance towards allogeneic solid organ grafts is one of the major goals in transplantation medicine. Mesenchymal stem cells (MSC) inhibit the proliferation of T cells in vitro, and thus are promising candidate cells to promote acceptance of transplanted organs in vivo. Such novel approaches of tolerance induction are needed since, to date, graft acceptance can only be maintained through lifelong treatment with unspecific immunosuppressants that are associated with toxic injury, opportunistic infections and malignancies. In our current work, we demonstrate that donor-derived MSC induce long-term allograft acceptance in a rat heart transplantation model, when concurrently applied with a short course of low-dose mycophenolate. The tolerogenic effect of MSC was mediated by the expression of indoleamine 2,3-dioxygenase (IDO), outlined by the fact that blocking of IDO with 1-methyl tryptophan (1-MT) abrogated graft acceptance. In this respect, MSC-mediated tolerance is different from donor leukocyte-mediated tolerance. The application of donor leucocytes also induced graft acceptance in our model, but not through IDO, since blocking of IDO did not result in graft rejection. In summary, we demonstrate that MSC constitute a promising tool for the induction of non-responsiveness in solid organ transplantation that warrants further investigation in clinical studies.