Abstract: ObjectiveTo explore the effect and mechanism of human adipose-derived mesenchymal stem cells (hADMSCs) on phenotypic polarization of microglia. MethodsBV-2 microglia of C57/BL6 mice were co-cultured with hADMSCs+lipopolysaccharide (LPS),or cultured with LPS alone. Cell morphology was observed under an inverted microscope. The effect of hADMSCs on microglial proliferation was evaluated by CCK-8 assay. The impact of hADMSCs on microglia M1/M2 phenotype markers were detected using quantitative real-time PCR (RT-qPCR). The affect of hADMSCs on the proteins expression levels of Toll-like receptor 4 (TLR4)-TIR domain containing adaptor protein inducing interferon β (TRIF) signaling pathway in BV-2 microglia was detected by using Western blot analysis. ResultsAs compared with the LPS treatment,hADMSCs treatment had no obvious effect on microglia morphology,whereas showed significant inhibition on microglial proliferation activity (P<0.05). Simultaneously,hADMSCs treatment reduced expression of microglia M1 phenotype markers (P<0.05),and increased microglia M1 phenotype markers in gene levels (P<0.05). At the same time,protein expression levels of TRIF,TLR4,phosphorylated interferon regulatory factor 3 (P-IRF3) and interferon regulatory factor 3 (IRF3) in BV-2 microglia were decreased after hADMSCs treatment. ConclusionhADMSCs can blockade the LPS-induced pro-inflammatory microglia M1 phenotype,whereas induces protective microglial M2 phenotype,which may be related to inhibition of the TLR4-TRIF signaling pathway.