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Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis
  1. L Xu1,*,
  2. A Y Hui1,,
  3. E Albanis1,
  4. M J Arthur1,§,
  5. S M O’Byrne2,
  6. W S Blaner3,
  7. P Mukherjee4,
  8. S L Friedman1,
  9. F J Eng1
  1. 1Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA
  2. 2Department of Medicine, Columbia University, New York, NY, USA
  3. 3Institute of Human Nutrition, Columbia University, New York, NY, USA
  4. 4Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY, USA
  1. Correspondence to:
    Professor S L Friedman
    Box 1123, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 11-70C, New York, NY10029, USA;


Background: Hepatic stellate cells (HSCs) are a major fibrogenic cell type that contributes to collagen accumulation during chronic liver disease. With increasing interest in developing antifibrotic therapies, there is a need for cell lines that preserve the in vivo phenotype of human HSCs to elucidate pathways of human hepatic fibrosis. We established and characterised two human HSC cell lines termed LX-1 and LX-2, and compared their features with those of primary human stellate cells.

Methods and results: LX-1 and LX-2 were generated by either SV40 T antigen immortalisation (LX-1) or spontaneous immortalisation in low serum conditions (LX-2). Both lines express α smooth muscle actin, vimentin, and glial fibrillary acid protein, as visualised by immunocytochemistry. Similar to primary HSCs, both lines express key receptors regulating hepatic fibrosis, including platelet derived growth factor receptor β (βPDGF-R), obese receptor long form (Ob-RL), and discoidin domain receptor 2 (DDR2), and also proteins involved in matrix remodelling; matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinase (TIMP)-2, and MT1-MMP, as determined by western analyses. LX-2 have reduced expression of TIMP-1. LX-2, but not LX-1, proliferate in response to PDGF. Both lines express mRNAs for α1(I) procollagen and HSP47. Transforming growth factor β1 stimulation increased their α1(I) procollagen mRNA expression, as determined by quantitative reverse transcription-polymerase chain reaction. LX-2, but not LX-1, cells are highly transfectable. Both lines had a retinoid phenotype typical of stellate cells. Microarray analyses showed strong similarity in gene expression between primary HSCs and either LX-1 (98.4%) or LX-2 (98.7%), with expression of multiple neuronal genes.

Conclusions: LX-1 and LX-2 human HSC lines provide valuable new tools in the study of liver disease. Both lines retain key features of HSCs. Two unique advantages of LX-2 are their viability in serum free media and high transfectability.

  • HSC, hepatic stellate cell
  • PDGF, platelet derived growth factor
  • βPDGF-R, PDGF receptor β
  • DDR2, discoidin domain receptor 2
  • Ob-RL, obese receptor long form
  • MMP, matrix metalloproteinase
  • TIMP, tissue inhibitor of matrix metalloproteinase
  • TGF-β1, transforming growth factor β1
  • BSA, bovine serum albumin
  • DMEM, Dulbecco’s modified Eagle’s medium
  • α-SMA, α smooth muscle actin
  • GFAP, antiglial fibrillary acid protein
  • FBS, fetal bovine serum
  • PBS, phosphate buffered saline
  • RT-PCR, reverse transcription-polymerase chain reaction
  • HPLC, high pressure liquid chromatography
  • fibrosis
  • wound healing
  • liver
  • myofibroblast
  • stellate cells

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  • * Present addresses: Shanghai University of TCM, Institute of Liver Diseases, Shuguang Hospital, Shanghai, China, 200032;

  • The Chinese University of Hong Kong, Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong;

  • § Office of the Dean, University of Southampton, Southampton, UK

  • Conflict of interest: None declared.