Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers

J Hepatol. 2002 Feb;36(2):200-9. doi: 10.1016/s0168-8278(01)00260-4.


Background/aims: Hepatic stellate cells (HSC) are commonly considered the precursor population of septal myofibroblasts (MF) in cirrhosis. We studied the distribution and expression profile of mesenchymal (myo)fibroblast-like populations in fibrotic and cirrhotic liver, in an attempt to elucidate their possible interrelationships.

Methods: Fibrotic/cirrhotic livers (from 22 human explants and from two rat models: carbon tetrachloride intoxication, bile duct-ligation) were studied by means of immunohistochemistry (single and double immunostaining) with antibodies raised against desmin, alpha-smooth muscle actin (alpha SMA), glial fibrillary acidic protein (GFAP), neural-cell adhesion molecule (N-CAM), synaptophysin, neurotrophins, neurotrophin receptors and alpha B-crystallin (ABCRYS).

Results: Septal MF showed the same expression profile as portal MF, in human and rat, being alpha SMA/ABCRYS/brain-derived nerve growth factor/GFAP-expression, with additional N-CAM- and desmin-expression in rat portal/septal MF. Perisinusoidally located HSC stained with all tested markers, MF at the septal/parenchymal interface showed an expression profile, intermediate between the profiles of HSC and portal/septal MF.

Conclusions: In advanced fibrosis and in cirrhosis, regardless of cause or species, three distinct mesenchymal (myo)fibroblast-like liver cell subpopulations can be discerned: portal/septal MF, interface MF and perisinusoidally located HSC. The fact that septal MF share more characteristics with portal MF than with HSC might suggest descent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Animals
  • Carbon Tetrachloride
  • Cholestasis, Extrahepatic
  • Fibroblasts / chemistry
  • Fibroblasts / pathology*
  • Glial Fibrillary Acidic Protein / analysis
  • Hepatocytes / chemistry
  • Hepatocytes / pathology*
  • Humans
  • Immunohistochemistry
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / pathology*
  • Male
  • Membrane Proteins
  • Neural Cell Adhesion Molecules / analysis
  • Rats
  • Rats, Wistar


  • Actins
  • Glial Fibrillary Acidic Protein
  • Membrane Proteins
  • Neural Cell Adhesion Molecules
  • ligatin
  • Carbon Tetrachloride