Precision-cut fibrotic rat liver slices as a new model to test the effects of anti-fibrotic drugs in vitro

Background/Aims Current cell culture models contributed significantly to the study of liver fibrosis and the testing of anti-fibrotic drugs but mimic the complex in vivo milieu poorly. Therefore, we evaluated fibrotic rat liver slices as a new, more physiologic in vitro model to test anti-fibrotic compounds. Methods Precision-cut slices (8mm diameter, 250μm thickness) were prepared from fibrotic rat livers three weeks after bile-duct ligation and incubated for 0–48h, during which viability and progression of the fibrotic process was evaluated. In addition, the effects of pentoxifylline, gleevec, and dexamethasone on mRNA expression of markers for fibrosis were determined. Results Fibrotic liver slices remained viable during 48h of incubation, with increasing α SMA and pro-collagen 1a1 mRNA expression, and αSMA and collagen protein content after prolonged incubation. Addition of pentoxifylline, gleevec, or dexamethasone during incubation dose-dependently inhibited pro-collagen-1a1 and αSMA mRNA expression after 24h of incubation without influencing slice viability. Conclusions Fibrotic liver slices are a promising tool to test anti-fibrotic drugs in vitro in a multicellular, fibrotic milieu, which cannot be achieved in vitro using other models. Importantly, this method may provide the opportunity to study anti-fibrotic compounds not only in animal but also in fibrotic human liver tissue.