Liver Fibrosis Model
Discover how Melior’s unique phenotypic screening platforms can uncover the untapped value of your candidate therapeutic
The two most commonly used animal models of liver fibrosis are induced chemically (carbon tetrachloride; CCl4) or by bile duct ligation (BDL). CCl4 causes hepatocyte damage, necrosis, inflammation, and fibrosis after 4 weeks of challenge and over 8 weeks causes cirrhosis. In contrast, BDL stimulates the proliferation of biliary epithelial cells and oval cells causing proliferating bile ductules with accompanying portal inflammation and fibrosis.
Liver fibrosis is a wound healing response to acute or chronic injury that results in the excessive deposition of extracellular matrix proteins, i.e., scar tissue. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension.
In animal models of liver fibrosis the insult induced by carbon tetrachloride (CCl4) resembles important properties of human liver fibrosis including inflammation, regeneration, and fiber formation. This model is commonly used to study acute liver injury, advanced fibrosis, as well as fibrosis reversal. Additionally, the CCl4 induced liver fibrosis model is highly reproducible and therefore an excellent candidate for drug screening.
The study summarized below illustrates the profound fibrotic phenotype of the CCl4 model. There is currently no approved therapeutic for treating this condition and accordingly no positive control for validating the model. Nonetheless it is an accepted essential model for evaluating anti-fibrotic candidate therapeutics.
These data illustrate the clinically relevant presentation of liver fibrosis in this animal model. The features described above are highly reminiscent of those seen in human liver fibrosis.