Rat liver myofibroblasts and hepatic stellate cells: Different cell populations of the fibroblast lineage with fibrogenic potential

Background & Aims: Hepatic stellate cells (HSCs) are considered the princip al matrix-producing cells of the damaged liver. However, other cell types o f the fibroblast lineage that have not yet been characterized are also invo lved in liver tissue repair and fibrogenesis. Methods: We established cultu res of cells of the fibroblast lineage, termed rat liver myofibroblasts, an d analyzed their phenotypical and functional properties in comparison with HSCs. Results: HSCs and rat liver myofibroblasts were discernible by morpho logical criteria and growth behavior. Prolonged subcultivation of rat liver myofibroblasts was achieved, but HSCs were maintained in culture at maximu m until second passage. HSCs were characterized by expression of glial fibr illary acidic protein, desmin, and vascular cell adhesion molecule 1, which were almost completely absent in rat liver myofibroblasts. For synthetic p roperties, HSCs and rat liver myofibroblasts displayed mostly overlapping p roperties with 4 striking differences. The complement-activating protease P 100 and the protease inhibitor alpha(2)-macroglobulin were preferentially e xpressed by HSCs, whereas interleukin 6-coding messenger RNAs and the extra cellular matrix protein fibulin 2 were almost exclusively detectable in rat liver myofibroblasts. Conclusions: The data show that morphologically and functionally different fibroblastic populations, HSCs and rat liver myofibr oblasts, can be derived from liver tissue. HSCs may not represent the singl e matrix-producing cell type of the fibroblast lineage in the liver.