Bone marrow mesenchymal stem cells suppress ascitogenous hepatoma progression in BALB/c mouse through reducing myeloid-derived suppressor cells

Abstract

Bone marrow mesenchymal stem cells (BMSCs) and myeloid-derived suppressor cells (MDSCs) can be mobilized from bone marrow (BM) into blood stream and home in tumor stroma, where they either help or hinder tumor growth. The issue of whether BMSCs could affect MDSCs in ascitogenous hepatoma BALB/c mice, thus influencing their functional activity, remains unclear. In this study, we demonstrated that after transfusion into ascitogenous hepatoma BALB/c mice, the homing fraction of BMSCs in BM was 2%-5% in 24-72 h and the percentage of Gr-1+CD11b+ MDSCs was downregulated in peripheral blood (PB) and BM. Meanwhile, IFN-γ+ T lymphocytes in PB increased. As a result of such immunoregulation, BMSCs treatment caused a delayed tumor growth and a prolonged survival in H22 ascitogenous hepatoma model. Because the proliferation of H22 cells was not affected by in vitro coculture with BMSCs, this observation is likely due to a systemic suppressive effect on the host MDSCs. We also demonstrated that BMSCs inhibited the induction and proliferation of MDSCs from hematopoietic stem cells (HSCs) in an in vitro tumor conditioned medium. Thus, our findings show for the first time that BMSCs are potentially inhibitor during MDSCs induction and proliferation and that when injected intravenously into tumor bearing mice they might be effective antitumor agents suitable for cancer therapy.

Keywords: Bone marrow mesenchymal stem cells; myeloid-derived suppressor cells; tumor.