Bone marrow mesenchymal stem cells suppress metastatic tumor development in mouse by modulating immune system.

Abstract

IntroductionBone marrow mesenchymal stem cells (BMSCs) have been studied extensively because of their potential use in clinical therapy, regenerative medicine, and tissue engineering. However, their application in tumor therapy remains yet in preclinical stage because of the distinct results from different researches and vagueness of their functional mechanism. In this study, the influence of BMSCs on tumor growth was observed and the potential mechanism was investigated.MethodTwo animal models, H22 ascitogenous hepatoma in BALb/c mouse and B16-F10 pulmonary metastatic melanoma in C57 mouse, were adopted in experience in vivo and treated with BMSCs by intravenous injection. The percentage of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) and IFN-γ+ T cells were observed in peripheral blood (PB) and bone marrow (BM) by Flow Cytometry. BMSCs were co-cultured in vitro with tumor cells and MDSCs in a tumor conditioned medium separately in order to illustrate the mechanism.ResultsOur results demonstrated that BMSCs treatment caused a delayed tumor growth and a prolonged survival in both tumor models, the homing fraction of BMSCs in BM was 2% - 5% in 24–72 hours after transfusion and the percentage of Gr-1+CD11b+ MDSCs was downregulated in peripheral blood and BM. Meanwhile, IFN-γ+ T lymphocytes in PB increased. In vitro co-culture showed that BMSCs inhibited the induction and proliferation of MDSCs in tumor conditioned medium, whereas they didn’t affect the proliferation of B16-F10 and H22 cells by in vitro co-culture. Both in vivo and in vitro results showed that BMSCs have a systemic suppressive effect on MDSCs.ConclusionOur data suggest that BMSCs has suppressive effect on tumor and is feasible to be applied in cancer treatment. BMSCs inhibiting MDSCs induction and proliferation is likely one of the mechanism.