title: Human bone marrow mesenchymal stem cells are resistant to HBV infection during differentiation into hepatocytes in vivo and in vitro.
abstract: Hepatocyte-like cells induced from bone marrow mesenchymal stem cells (BMSCs) recover liver function in animal models with liver failure. Our initial findings revealed that human BMSCs improved liver function in hepatitis B patients with end stage liver disease. However, the susceptibility of BMSCs to HBV infection during induction toward hepatocytes remains unknown. We have assessed whether BMSCs-derived hepatocyte-like cells can function like liver cells and be infected by HBV. A new and efficient way to direct the differentiation of BMSCs into functional hepatocytes was developed. BMSCs obtained from hepatitis B patients were induced to differentiate into hepatocytes through exposure to HGF, FGF-4, and EGF. After 6 days of exposure, BMSCs-derived hepatocyte-like cells that expressed a subset of hepatic genes and showed hepatic functions were obtained. HBV was used to infect the differentiated cells, and subsequently these cells were assayed for the presence of HBeAg, HBsAg, and HBV DNA. BMSCs proved resistant to HBV infection, both in vitro and during differentiation into hepatocytes in vitro. This demonstrates that BMSCs are resistant to HBV infection. BMSCs are viable for transplantation and should facilitate further research exploring the in vivo HBV-resistance of the hepatocytes derived from BMSCs after transplantation, a characteristic that could form the basis for hepatocyte transplantation.
authors.affiliation: Department of Infectious Disease, Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, PR China.
authors.forename: Chan
authors.initials: C
authors.lastname: Xie
authors.forename: Yu-Bao
authors.initials: YB
authors.lastname: Zheng
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Zhu
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.forename: Zhi-Liang
authors.initials: ZL
authors.lastname: Gao
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D004279:DNA, Viral / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051519:Fibroblast Growth Factor 4 / Q000494:pharmacology; D006509:Hepatitis B / Q000628:therapy*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000637:transplantation / Q000821:virology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology*
chemical_list: D004279:DNA, Viral; D051519:Fibroblast Growth Factor 4; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor