Enhanced growth and hepatic differentiation of fetal liver epithelial cells through combinational and temporal adjustment of soluble factors

Biotechnol J. 2012 Mar;7(3):440-8. doi: 10.1002/biot.201100184. Epub 2011 Oct 26.


Fetal liver epithelial cells (FLEC) are valuable for liver cell therapy and tissue engineering, but methods for culture and characterization of these cells are not well developed. This work explores the influence of multiple soluble factors on FLEC, with the long-term goal of developing an optimal culture system to generate functional liver tissue. Our comparative analysis suggests hepatocyte growth factor (HGF) is required throughout the culture period. In the presence of HGF, addition of oncostatin M (OSM) at culture initiation results in concurrent growth and maturation, while constant presence of protective agents like ascorbic acid enhances cell survival. Study observations led to the development of a culture medium that provided optimal growth and hepatic differentiation conditions. FLEC expansion was observed to be approximately twofold of that under standard conditions, albumin secretion rate was 2-3 times greater than maximal values obtained with other media, and the highest level of glycogen accumulation among all conditions was observed with the developed medium. Our findings serve to advance culture methods for liver progenitors in cell therapy and tissue engineering applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / metabolism
  • Animals
  • Ascorbic Acid / administration & dosage
  • Cell Culture Techniques / methods*
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Culture Media / chemistry
  • Epithelial Cells / cytology*
  • Glycogen / metabolism
  • Hepatocyte Growth Factor / administration & dosage
  • Liver / cytology
  • Liver / embryology*
  • Liver / growth & development*
  • Mice
  • Mice, Inbred C57BL
  • Oncostatin M / administration & dosage
  • Tissue Engineering


  • Albumins
  • Culture Media
  • Oncostatin M
  • Hepatocyte Growth Factor
  • Glycogen
  • Ascorbic Acid