Characterization of human hepatic and biliary and their potential role in the pathophysiology of liver and biliary tree
In the liver, hepatic stem/progenitor cells (HPCs or HpSCs) represent a facultative stem/progenitor cell compartment located within the smaller branches of intrahepatic biliary tree. HPCs are bipotential stem cells characterized by the capability to differentiate towards mature hepatocytes and cholangiocytes. In different chronic human liver diseases, HPCs activate and proliferate as a consequence of impaired proliferation of mature parenchymal liver cells by a variety of insults. Beside the HPC niche, endoderm-like stem cells have been recently described within extrahepatic and large intrahepatic bile ducts. These Biliary Tree Stem Cells (BTSCs) are located within peribiliary glands.
The general aim of the present project will be to investigate the role of hepatic and biliary tree stem cells in human pathologies and the activation of specific signaling pathways. Specific objectives of the present project will be: i) to investigate the activation of hepatic progenitor cells (HPCs) in the progression of Non-Alcoholic Fatty Liver Diseases (NAFLD) and the relationship with levels of Lipopolysaccharide (LPS) and adipokines; ii) to study the signaling pathways driving the stem cell activation in human cholangiopathies; iii) to individuate the role of peribiliary glands (PBGs) in the pathogenesis of biliary strictures after liver transplantation and in the development of cholangiocarcinoma (CCA) in Primary Sclerosing Cholangitis (PSC).
Data that will be obtained from this the project will be useful to understand cellular mechanisms at the basis of NAFLD and cholangiopathy progression and could individuate novel molecular tools and cellular target for therapeutic approaches. Investigations on the mechanisms driving stem cell activation and differentiation in liver diseases could help the development of potential therapeutic strategies triggering stem cell niches.