Regulation of mesenchymal stem cells derived from umbilical cord on natural killer cells-mediated cytotoxicity against dendritic cells / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect of mesenchymal stem cells derived from umbilical cord (UC-MSCs) on natural killer (NK) cells-mediated cytotoxicity against dendritic cells (DCs) and explore the mechanism.</p><p><b>METHODS</b>MSCs were isolated from human umbilical cord by collagen digestion and cultured in vitro. NK cells were separated from healthy human peripheral blood by magnetic bead sorting. Mononuclear cells from healthy human peripheral blood were cultured in the presence of granulocyte and macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to obtain the immature DCs. The DCs were then co-cultured with UC-MSCs in the presence of tumor necrosis factor α (TNFα) for 2 days, and the expressions of CD11c and CD86 on DCs and IL-12 level in the culture medium was detected using flow cytometry and ELISA, respectively. The cytotoxicity of NK cells against DCs was analyzed by LDH-releasing assay, and the expressions of ligands for killer activator receptor (MICA/B and ULBP1-3) on the DCs were detected with flow cytometry.</p><p><b>RESULTS</b>Compared with the cytokine-induced DCs, the DCs induced by co-culture with UC-MSCs showed an identical CD11c expression but lowered CD86 expression and IL-12 secretion. The natural killer cells produced a stronger cytotoxicity against UC-MSCs-induced DCs than against cytokine-induced DCs. The UC-MSCs-induced DCs also showed increased expressions of MICA and MICB on the surface.</p><p><b>CONCLUSION</b>UC-MSCs can enhance NK cells-mediated cytotoxicity against DCs possibly by inhibiting DC maturation and up-regulating the ligands for killer activator receptor on the surface of the DCs.</p>