Ricerc@Sapienza

Background and Aims: Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by inflammation and bile duct fibrosis. Massive proliferation of biliary tree stem/progenitor cell (BTSC), expansion of peribiliary glands (PBG) and dysplasia were observed in PSC. Cholangiocarcinoma (CCA) frequently complicates the course of PSC. The aims of the present study were to evaluate the involvement of PBGs and BTSCs in CCA emerging in PSC patients.

Peribiliary glands (PBGs) represent the niche of biliary tree stem/progenitor cells (BTSCs) [1]. BTSCs are multipotent stem cells able to differentiate into hepatocytes, cholangiocytes, and pancreatic islets. Primary sclerosing cholangitis (PSC) is a chronic inflammation involving extra-hepatic biliary tree, and is complicated by the risk of cholangiocarcinoma (CCA) development [2]. We aimed to evaluate the involvement of PBGs and BTSCs in PSC and their role in CCA insurgence [2].

Two distinct stem/progenitor cell populations of biliary origin have been identified in the adult liver and biliary tree. Hepatic Stem/progenitor Cells (HpSCs) are bipotent progenitor cells located within the canals of Hering and can be differentiated into mature hepatocytes and cholangiocytes; Biliary Tree Stem/progenitor Cells (BTSCs) are multipotent stem cells located within the peribiliary glands of large intrahepatic and extrahepatic bile ducts and able to differentiate into hepatic and pancreatic lineages.

Background and Aims: Mechanisms underlying the repair of extrahepatic biliary tree (EHBT) after injury have been scarcely explored. The aims of this study were to evaluate, by using a lineage tracing approach, the contribution of peribiliary gland (PBG) niche in the regeneration of EHBT after damage and to evaluate, in vivo and in vitro, the signaling pathways involved. Approach and Results: Bile duct injury was induced by the administration of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 14 days to Krt19CreTdTomatoLSL mice.