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Two new immortal lines of human hepatic stellate cells are set to revolutionise research of chronic liver disease, maybe leading to antifibrotic treatments, reports a team in the United States. Future research can now rely on a ready, stable source of cells free of species differences and a need for external serum for growth, both potential confounders.
The cell lines were obtained from isolated stellate cells from normal liver tissue, one by SV40 T antigen immortalisation (LX-1) and the other by spontaneous immortalisation after selecting from LX-1 for growth in low serum concentration (LX-2). A range of molecular tests established their properties. LX-1 and LX-2 were strongly similar in overall gene expression to mature human stellate cells (98% and 99%, respectively), according to microarray analyses. Their phenotype was similar to that of activated stellate cells in vivo. Both cell lines expressed key receptors for regulating liver fibrosis and proteins linked to matrix remodelling. Both expressed mRNA for fibrillar type I collagen characteristic of fibrosis, and the cytokine transforming growth factor (TFG) β1 stimulated expression of a collagen precursor. LX-2 cells expressed less tissue inhibitor of matrix metalloproteinase (TIMP)-2, like primary human stellate cells, but, in contrast, showed high transfection rates and ability to grow in low serum containing media.
Hepatic stellate cells, formerly lipocytes, are responsible for liver fibrosis once activated. Understanding the exact process of fibrosis has, until now, been hampered by the erratic availability of human stellate cells and their variability and by inevitable doubts about validity of results obtained in other models, mostly rat cell cultures.
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