Precision-Cut Liver Slices: A Valuable Preclinical Tool for Translational Research in Liver Fibrosis

Halting liver fibrosis progression is a key goal in treating liver disease, yet effective antifibrotic drugs remain unavailable. This study explores the use of precision-cut liver slices (PCLS) as an ex vivo model to evaluate new therapies. Researchers tested how different oxygen levels affect viability, tissue integrity, and inflammatory response in PCLS from healthy and fibrotic rats. Fibrotic PCLS maintained their pathological gene signature under 40% oxygen and responded to inflammatory stimuli, indicating preserved functionality. Exposure to high oxygen levels increased oxidative stress and pro-inflammatory gene expression. Cirrhotic PCLS showed early signs of reduced viability and the upregulation of fibrosis-related genes including <i>Col1α2</i>, <i>Col3α1</i>, <i>αSMA</i>, <i>Timp1</i>, <i>Timp2</i>, <i>Mmp2</i>, <i>Pdgfrβ</i>, <i>Nos2</i>, <i>Cox2</i>, and <i>Il6</i>. Lipopolysaccharide (LPS) exposure induced the marked overexpression of <i>Nos2</i> and <i>Il1β</i> mRNA and confirmed the model's responsiveness to external injury. Fibrotic PCLS retained fibrogenic activity for at least 48 h. Additionally, the adenoviral delivery of a dominant-negative soluble PDGFRβ effectively blocked fibrotic signaling. Human fibrotic PCLS also remained viable for 72 h and showed an increased mRNA expression of fibrosis markers such as <i>COL1A1</i>, <i>αSMA</i>, and <i>MMP2</i>. These results highlight the potential of PCLS as a promising platform for future therapeutic testing, pending further validation with functional interventions.