In the liver, Hepatic stem/progenitor cells (HPCs or HpSCs) represent a resident stem/progenitor cell compartment located within the smaller branches of intrahepatic biliary tree. HPCs are bipotential stem cells characterized by 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 specific aims of the present project will be: i) to investigate the role of hepatic progenitor cells (HPCs) in the progression of Non-alcoholic Fatty Liver Diseases and its relationship with macrophage and myofibroblast pool; ii) to study the niche of Biliary Tree Stem Cells (BTSC) in peribiliary glands, in pancreatic duct glands, and in Brunner¿s Glands in duodenum; iii) to study the involvement of BTSCs in biliary damage during primary sclerosing cholangitis (PSC) and BTSC role in the pathogenesis of cholangiocarcinoma in primary sclerosing cholangitis patients.
Investigations on the mechanisms driving stem cell activation and differentiation in the course of liver diseases could help the development of potential therapeutic strategies triggering stem cell niches. A better knowledge on the patho-physiology of stem cell niche could help to optimize the strategies for stem cell isolation including, the best markers for cell sorting or the best portion of biliary tree , pancreatic ducts, or duodenum to be used for BTSC isolation.
