The Effect Of Human Mesenchymal Stem Cell On The Property Of Monocyte-derived Dendritic Cell

Several studies have shown that mesenchymal stem cells (MSCs) harbor animmunoregulatory activity; they can inhibit T lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Although MSCs can perform a direct immunosuppressive effect on T cells proliferation in vitro, it is unclear whether they also modulate the immune system by acting on the very first step of the immune response.In this investigation we first isolated MSC from human bone marrow and study their morphology, phenotype and function. As reported before, MSC can inhibit cellular or nonspecific mitogenic stimuli induced T cell proliferation with a dose-dependent manner. Next we developed DC from CD 14+ monocyte and the morphology, phenotype and function were studied. Finally, we addressed the effects of human MSCs on differentiation, maturation, and function of dendritic cells (DCs) from CD 14+ monocytes in vitro. Our data showed that MSCs coculture inhibited the initial differentiation of monocytes to DCs upon induction with GM-CSF and IL-4 in a strong but reversible fashion. Cell-cell contact and soluble factors were involved in this inhibition with cellular contact played a more important role. Different from other report, IL-6 and M-CSF were not the sole factors in the effect of MSC on DC, which suggests that alternative or additional growth factors generated by MSC played a role in governing DC development relative to those used to generate DC with defined cytokines. Furthermore, mature DCs treated with MSCs displayed a significant reduction in expression of HLA-DR, CD la, and costimulatory molecules CD80/CD86 without acquisition of CD 14. Functionally, MSCs treatment resulted in impairment of allostimulatory ability of mature DCs, correlating well with reduction of IL-12 secretion.In conclusion, our data suggested for the first time that human MSCs could successively suppress bipotential monocytes into DCs, the most potent antigen-presenting cells (APCs), to modulate the ultimate specific immune response.