Behavior of a cell line derived from normal human hepatocytes on non-physiological and physiological-type substrates: Evidence for enhancement of secretion of liver-specific proteins by a three-dimensional growth pattern

  • Matthew Smalley
  • Kenneth Leiper
  • David Floyd
  • Margaret Mobberley
  • Tim Ryder
  • Clare Selden
  • Eve A. Roberts
  • Humphrey Hodgson
Cellular Models


The behavior of a recently described cell line, HH25, derived from normal human hepatocytes, has been investigated on several different substrates—tissue-culture plastic, glass, a thin layer of rat-tail collagen I, and thin layers or thick gels of extracellular matrix derived from the Engelbreth-Holm-Swarm murine sarcoma (EHS matrix). Cellular morphology, proliferation, and secretion of three hepatocyte-specific proteins (albumin, α1 acid glycoprotein, and α1 antitrypsin) have been examined. There were no differences in morphology, proliferation, or differentiated function in the cells on either plastic, glass, collagen, I, or a thin layer of EHS matrix, but on a thick EHS matrix gel the cells altered their morphology (forming three-dimensional colonies with canalicular-like structures) and their production of albumin and α1 acid glycoprotein was enhanced. This suggests that the enhanced differentiated function is associated with the morphological change (occurring only on the thick EHS gel) rather than with receptor-mediated cell-matrix interactions (which can also occur on the thin layer of EHS matrix). This cell line is therefore a good in vitro cellular model for the investigation of the roles of morphological changes and of cell-cell and cell-matrix interactions in the control of human hepatocyte behavior without the need for an extensive source of primary tissue.

Key words

EHS matrix morphology differentiation albumin canaliculi 


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Copyright information

© Society for In Vitro Biology 1999

Authors and Affiliations

  • Matthew Smalley
    • 1
  • Kenneth Leiper
    • 1
  • David Floyd
    • 1
  • Margaret Mobberley
    • 2
  • Tim Ryder
    • 2
  • Clare Selden
    • 1
  • Eve A. Roberts
    • 3
  • Humphrey Hodgson
    • 1
  1. 1.Liver Group Laboratory, Department of MedicineRoyal Postgraduate Medical School, Hammersmith HospitalLondonUnited Kingdom
  2. 2.Electron Microscopy Unit, Department of PathologyQueen Charlotte’s and Chelsea HospitalLondonUnited Kingdom
  3. 3.Division of Gastroenterology and Nutrition, The Hospital for Sick Children Research InstituteUniversity of TorontoTorontoCanada

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