Transforming Growth Factor-β Partially Reversed the Immunosuppressive Effect of Mesenchymal Stem Cells in Mice

Abstract

BackgroundMesenchymal stem cells (MSCs) possess powerful immunosuppression capacity. Transforming growth factor-β (TGF-β) is a well-known anti-inflammatory cytokine and plays an important role in various inflammatory processes. We hypothesized that TGF-β could synergize with MSCs in suppressing immune responses, and therefore established a mouse skin graft model to evaluate the effect of MSCs and MSCs combined with TGF-β on transplantation immunity in vivo. MethodsBalb/c and C57BL/6 mice were used to establish the skin graft model. The recipients were divided into 3 groups and received intravenous bone marrow mesenchymal stem cells (BMSCs), BMSCs pretreated with TGF-β, and 0.9% saline solution, respectively. Skin graft survival time, pathological detection, the ratio of CD4+CD25+Foxp3+Treg cell of spleens, and the level of IFN-γ, IL-2, IL-10, and TGF-β expression were tested. ResultsThe survival time of skin grafts were prolonged in both BMSC (12.5 ± 1.35 days) and BMSC-TGF-β (10.6 ± 1.90 days) recipients compared to the blank control recipients (8.0 ± 1.05 days). The ratio of CD4+CD25+Foxp3+Treg cell of spleens from BMSC and BMSC-TGF-β recipients was higher than that of the blank control, and the upregulated proliferation in the BMSC group occurred earlier and was prolonged compared to the BMSC-TGF-β group. The expression of IFN-γ and IL-2 was inhibited in both the BMSC and BMSC-TGF-β groups compared to the blank, while the expression of IL-10 and TGF-β was boosted. In contrast to the BMSC group, the BMSC-TGF-β group exhibited a weaker effect on the expression of cytokines. ConclusionTGF-β partially reversed the immunosuppressive effect of MSCs in vivo. This immunoregulatory feature may have potential applications for treating transplant rejection.