Operational transplant acceptance induced by mesenchymal stem cells - beyond early effects of donor antigen

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Immunomodulatory mesenchymal stem cell (MSC) therapy is a novel approach to complement standard pharmacotherapy to achieve the acceptance of solid organ allografts. In our previous work we have described a multitude of features of such tolerogenic stem cell effects, including the dose, route and timing of cell infusions, the role of donor antigen and antigen presenting cells in the process, the necessity of concurrent immunosuppression, the transferability of tolerance, the emergence of intermediate cell types and the generation of regulatory cells. Experiments suggested in this proposal will clarify the influence that MSC have on myeloid derived suppressor cells which govern the balance between Th17-type and T regulatory T cells.