Cholangiocarcinomas: New Insights from the Discovery of Stem Cell Niches in Peribiliary Glands of the Biliary Tree

Figure 3

Liver stem cell niches and cholangiocarcinoma classification based on cells of origin. Hepatic stem cell niches containing human hepatic stem cells (hHpSCs) (red stars) are located in adult liver, within the canals of Hering or in activated interlobular bile ducts. Biliary tree stem cell niches containing human biliary tree stem/progenitor cells (hBTSCs) (blue stars) are located in peribiliary glands (PBGs). PBGs start at the level of septal intrahepatic bile ducts where glands can be observed occasionally as small evaginations of the bile duct epithelium, with the interlobular bile ducts being devoid of glands. In the extrahepatic biliary tree, PBGs are present along the entire bile ducts, including the hepato-pancreatic common duct. Gallbladder is devoid of PBGs, while cystic duct wall has the same histological features of the other extrahepatic bile ducts. The existence of two different stem cell compartments and the associated cell lineages may result in multiple cells of origin of cholangiocarcinoma (CCA). Mixed-CCA could be considered the CCA subtype originating from hHpSC-derived lineages. Mucin IH-CCA, perihilar CCA, and distal EH-CCA could be considered the CCA subtypes originating from hBTSC derived lineages. The figure is a modification (with permission) of a figure prepared by Ms. Gemma Mendel for the review article referenced as [44].