The Regulation Of HUC-MSCs To Nerve Inflammation And Neural Stem Cells Differentiation

Objectives The occurrence of radiation-related cognitive impairment is mainly related to neurogenesis decreased and chronic inflammation of the nervous system caused by excessive activation of microglial cells, so we observe the effects of h UC-MSCs on the microglia proliferation and activation and on neural stem cells differentiation to study the regulation of h UC-MSCs to nerve inflammation and neurogenesis, which will provide new ideas for clinical treatment of radiation-related cognitive impairment, as well as open up new areas of mesenchymal stem cells' clinical applications.Methods We imitate nerve inflammation by stimulating BV2 microglia with lipopolysaccharide(LPS). BV2 cells was co-cultured with h UC-MSCs-CM and(or) LPS, after 24 or 48 h, BV2 proliferation was analyzed by MTT colorimetric method; TNF-a and IL-6 in BV2 cells supernatant was measured by ELISA kit; Arginase 1(Arg1) protein and m RNA was examined by Western blot and real-time PCR, respectively; TNF-a and IL-6 m RNA expression level was tested by real- time PCR. We made NE-4C cells co-cultured with M1 or M2 microglia respectively in transwell chambers, after 48 h, GFAP??3-Tubulin and ?-catenin protein was examined by Western blot.Results To LPS long time stimulation, BV2 showed obvious proliferation effect, however h UC-MSCs-CM can inhibit this response; BV2 cultured with LPS express high level TNFa and IL-6, while in both h UC-MSCs-CM and LPS conditions, the level of TNF-a and IL-6 was lower than LPS group; The level of Arg1 was increased in BV2 cells that was cocultured with h UC-MSCs-CM 48 h. The GFAP and ?-catenin protein was increased in NE-4C cells co-cultured with M2 microglia, but the ?3-Tubulin protein have no change.Conclusions Human UC-MSCs inhibit microglia proliferation caused by inflammation stimulation. Human UC-MSCs through paracrine mechanism reduced proinflammatory factor expression. Human UC-MSCs induce microglial cells to M2 polarization. M2 type microglia promote neural stem cell differentiation by activating Wnt/?-catenin pathway.