MSCs are arising as promising tool in solid organ transplantation to down regulate alloimmune responses. Defining the function and ways to monitor its immunologic effects is of great importance for the further development of MSC therapy. Although evidence from experimental models demonstrates that MSCs can inhibit immune responses, relevant clinical information is still limited. Recently we performed a safety and feasibility study in 6 kidney allograft recipients who received two IV infusions (1 million cells/kg) of autologous bone marrow MSCs, because of rejection and/or an increase in interstitial fibrosis/ tubular atrophy in the renal biopsy > 6 month after transplantation. Interestingly, 2 patients had a complete resolution of rejection after MSC treatment. Here we report results of extensive immune monitoring of the 6 MSC treated patients up to 12 weeks after MSC infusions in order to understand mechanisms involved. Total numbers of T cells, CD4/CD8 ratio, naÏve and memory CD4+ T cells and Tregs did not demonstrate consistent differences before and after MSC treatment. Similarly naÏve, EM-, CM CD8+ T cells, NK cells, B cell and total and inflammatory monocytes were equal before and after MSC treatment. For functional read out, mixed lymphocyte reaction (MLR) was used with donor and 3rd party (3P) peripheral blood mononuclear cells (PBMC) before and after MSC infusion and proliferation and different cytokines were measured. Five of the 6 patients demonstrated a reduction in PBMC proliferation 12 weeks after MSC infusion upon stimulation with donor specific PBMCs, while the response to 3P PBMCs was more variable. This donor specific reduction was not observed in patients without MSC infusions at similar time points post transplantation. IFN-g, IP-10 and MCP-1 levels measured in the supernatants of the PBMC proliferation assay declined upon stimulation with donor specific PBMC in 4 patients, while a similar decline was not observed in the 3P response. In conclusion, a donor specific down regulation of the MLR was observed in MSC treated patients, which emphasizes the importance of the MLR to monitor immunologic effects in patients after MSC therapy.
To cite this abstract in AMA style:Reinders M, de J, Roelofs H, de D, Claas F, van P, Roelen D, van C, Rabelink T. Treatment of Renal Transplant Patients with Autologous Bone Marrow Derived Mesenchymal Stromal Cells Downregulates the Donor Specific Mixed Lymphocyte Reaction [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/treatment-of-renal-transplant-patients-with-autologous-bone-marrow-derived-mesenchymal-stromal-cells-downregulates-the-donor-specific-mixed-lymphocyte-reaction/. Accessed September 23, 2017.
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