title: Engrafted human stem cell-derived hepatocytes establish an infectious HCV murine model.
abstract: The demonstrated ability to differentiate both human embryonic stem cells (hESCs) and patient-derived induced pluripotent stem cells (hiPSCs) into hepatocyte-like cells (HLCs) holds great promise for both regenerative medicine and liver disease research. Here, we determined that, despite an immature phenotype, differentiated HLCs are permissive to hepatitis C virus (HCV) infection and mount an interferon response to HCV infection in vitro. HLCs differentiated from hESCs and hiPSCs could be engrafted in the liver parenchyma of immune-deficient transgenic mice carrying the urokinase-type plasminogen activator gene driven by the major urinary protein promoter. The HLCs were maintained for more than 3 months in the livers of chimeric mice, in which they underwent further maturation and proliferation. These engrafted and expanded human HLCs were permissive to in vivo infection with HCV-positive sera and supported long-term infection of multiple HCV genotypes. Our study demonstrates efficient engraftment and in vivo HCV infection of human stem cell-derived hepatocytes and provides a model to study chronic HCV infection in patient-derived hepatocytes, action of antiviral therapies, and the biology of HCV infection.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Carpentier
authors.forename: Abeba
authors.initials: A
authors.lastname: Tesfaye
authors.forename: Virginia
authors.initials: V
authors.lastname: Chu
authors.forename: Ila
authors.initials: I
authors.lastname: Nimgaonkar
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.forename: Seung Bum
authors.initials: SB
authors.lastname: Lee
authors.forename: Snorri S
authors.initials: SS
authors.lastname: Thorgeirsson
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Feinstone
authors.forename: T Jake
authors.initials: TJ
authors.lastname: Liang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000502:physiology; D016174:Hepacivirus; D006526:Hepatitis C / Q000821:virology*; D022781:Hepatocytes / Q000637:transplantation* / Q000821:virology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology; D008099:Liver / Q000473:pathology / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D014764:Viral Proteins