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In vitro liver models have emerged as excellent tools to better understand liver pathology, to test new therapeutic drugs and for toxicity testing studies. In our group we are interested in generating better liver cells for the development of in vitro liver models. In this regard, we have developed a methodology to differentiate hepatic stellate cells from iPSC and we have shown their potential to model liver fibrosis and for toxicity studies. Our aim is to develop 3D multicellular in vitro systems to mimic liver diseases such as alcoholic and nonalcoholic steatohepatitis.
Liver cell plasticity
The liver has remarkable cell plasticity. Lineage tracing studies have shown the potential of biliary-to-hepatocyte as well as hepatocyte-to-biliary conversion in response of liver injury. This is particular important in the context of chronic liver diseases, which are characterized by an expansion of ductular reaction cells. Ductular reaction is a poorly characterized heterogeneous cell population comprising reactive cholangiocytes as well as immature liver progenitor cells, which may derive from both hepatocyte and biliary compartment.
Our laboratory is interested in understanding the maintenance of cell identity in liver injury and the role and impact of ductular reaction in disease progression. Moreover, we are particularly interested in understanding the association of the ductular reaction with liver regeneration, inflammatory response and fibrosis progression.
Mechanisms of liver inflammation and fibrosis
Chronic liver injury is characterized by an important inflammatory response and an increase in extracellular matrix deposition, which may lead to liver fibrosis and eventually cirrhosis. We are interested in identifying cellular and molecular mechanisms regulating the inflammatory response and liver fibrogenesis in chronic liver injury. Moreover, our laboratory is exploring how immune cell dysfunction affects liver injury and liver disease progression.
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