Fibrogenic cell fate during fibrotic tissue remodelling observed in rat and human cultured liver slices

Background/Aims Fibrotic liver remodelling was studied in culture of precision-cut liver slices (PCLS) derived from fibrotic liver. Methods Fibrosis was induced in rats by carbon tetrachloride (CCl4) treatment or bile duct ligation. Human fibrotic livers were also used. PCLS were cultured for 6, 24, 48, or 72 h, and the expression of α-smooth muscle (SM) actin, platelet-derived growth factor (PDGF) receptor-β, and active caspase 3 was studied by immunohistochemistry. Results Before culture, in CCl4-treated or bile duct ligated animals, fibrosis was observed around centrolobular veins, or in portal zones, respectively. In PCLS derived from CCl4-treated animals, α-SM actin expression disappeared after 24 h in culture while PDGF receptor-β expression decreased progressively after 48 h. These changes were observed in absence of massive apoptosis. In PCLS derived from bile duct ligated animals, both α-SM actin and PDGF receptor-β expression decreased after 48 h in culture with a massive apoptosis. In PCLS derived from human fibrotic livers, α-SM actin expression was dramatically reduced after 48 h in culture. Conclusions After CCl4 treatment, a proportion of myofibroblasts derived from hepatic stellate cells seems to dedifferentiate while in bile duct ligation model, myofibroblasts derived from portal fibroblasts disappear by apoptosis, underlining the relevance of this model to evaluate the mechanisms involved in fibrotic liver remodelling.