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Human hepatic stellate cells and hepatocyte co‐cultures maintain differentiation in vitro and in vivo
Author(s) -
Harding Martha J,
Barnaeva Elena,
Bustamante Marcia,
Lepus Christin M,
Rahner Christoph,
Pober Jordan S,
Sjogren Maria H,
Rojkind Marcos
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.465.3
Subject(s) - hepatic stellate cell , in vivo , biology , in vitro , hepatocyte , liver cytology , albumin , medicine , endocrinology , biochemistry , microbiology and biotechnology , liver metabolism
Lack of long‐term cultures of mature human hepatocytes (Hep) that maintain liver‐specific functions have hampered investigations of the effects of chronic drug toxicity and liver pathogens. We investigated if matrix‐producing hepatic stellate cells (HSC) sustained Hep survival and differentiation in vitro and in vivo . Co‐cultures (CC) survived 2 months in vitro , maintained expression of albumin, CYP2E1, CD81, and CK19 mRNAs, began to express α‐fetoprotein and secreted α1‐antitrypsin and fibrinogen. CC proliferated and required passaging every 3–4 weeks. CC prepared with Hep from newborn subjects expressed and sustained the hepatoblast markers Thy1 and Sca 1 in vitro . Transplanted Hep survived in CC for at least 8 weeks when engrafted in vascularized protein gels on the abdominal wall of SCID/bg mice. EM revealed that Hep ultrastructure and polarization was preserved and groups of epithelial cells formed bile duct‐like structures in vivo . Our findings suggest that Hep‐HSC CC sustain normal Hep morphology and differentiation. Accordingly, these CC could be used in studies of liver repopulation, hepatitis infections and long‐term toxicity of drugs and alcohol. Supported by AGA RSA (MJH), NIH‐R01HL085416 (JSP), USUHS MDA905‐03‐1‐0006 (MHS) and NIH‐RO1AA10541(MR) grants.