Test efficacy of anti-fibrotic drugs in a clinically relevant 3D disease model
Various stimuli such as viral infection, drugs, alcohol and toxicants can damage hepatocytes, and activate Kupffer cells and hepatic stellate cells (HSCs). This damage can lead to development of liver fibrosis, characterized by the accumulation of extracellular matrix (ECM). Activation of HSCs and their trans-differentiation from quiescent, vitamin-A-storing cells into proliferative, fibrogenic myoﬁbroblasts is well established as a central driver of fibrosis in experimental and human liver injury. Activated HSC express smooth muscle actin and ECM proteins such as collagens type I, III, IV, and fibronectin. The 3D InSight™ Human Liver Fibrosis Model is a liver microtissue model containing the primary hepatocytes, HSCs, Kupffer cells, and liver endothelial cells (LECs) that are susceptible to induction to fibrosis, and suitable for efficacy testing of disease inhibiting or disease reverting drugs.
- Test induction and prevention of liver fibrosis through activation or in-activation of hepatic stellate cells
- Study fibrosis-related cell parameters, including HSC activation, ECM deposition, and changes in pro-inflammatory and pro-fibrotic marker mRNA and protein expression levels
- Perform efficacy screening of anti-fibrosis drugs in high-throughput compatible and cost-effective platform
Detecting the liver fibrosis disease state with mRNA expression of pro-fibrogenic markers. Data shows 7-day exposure to TGF-β induces fibrosis in the 3D InSight™ Human Liver Fibrosis Model, which HSCs, which are activated by pro-fibrotic stimuli, such as TGF-β, as well as Kupffer cells and liver endothelial cells, which influence liver fibrosis. This fibrotic state is detected by increased expression of pro-fibrogenic markers: stellate-cell activation marker ACTA2; ECM markers COL1A1, COL3A1, and COL41; early fibrosis marker LOX2; and stellate activation marker PDGFβ.
Find out how you can accelerate anti-fibrotic drug discovery with an advanced 3D liver disease model.