Objective:To investigate whether in vitro cultured human bone marrow mesenchymal stem cells (BMSCs) express sodium taurocholate cotransporting polypeptide (NTCP), assess their susceptibility to hepatitis B virus (HBV) infection and analyze the role of NTCP during HBV infection. Methods:BMSCs were infected with HBV-positive serum under different conditions. HBV DNA load in cell culture supernatants as well as in BMSCs and the amount of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) in cell culture supernatants were detected. To analyze the role of NTCP, BMSCs were first transfected with small interfering RNA targeting NTCP (NTCP-siRNA) and then infected with HBV-positive serum under different conditions. Virus loads and the amount of HBsAg and HBsAg were also detected. Western blot assay was performed to measure the expression of NTCP in BMSCs in each group.Results:In vitro cultured adherent BMSCs were susceptible to HBV infection albeit with a really low efficiency, but the infection efficiency was significantly increased when infecting the BMSCs in suspension. NTCP was expressed in BMSCs and the expression could be upregulated during HBV infection, especially in BMSCs in suspension. HBV infection was blocked when BMSCs were transfected with NTCP-siRNA. Conclusions:In vitro cultured human BMSCs were susceptible to HBV infection and the expressed NTCP served as a functional receptor for HBV. Human BMSCs could be used as a highly susceptible and stable cell model that needed no molecular adjuvant modification for research on the early stages of the HBV life cycle and for development of antiviral therapy.