Biliary stem cells in health and cholangiopathies and cholangiocarcinoma.

Abstract

This review discusses evidence regarding progenitor populations of the biliary tree in the tissue regeneration and homeostasis, and the pathobiology of cholangiopathies and malignancies. In embryogenesis biliary multipotent progenitor subpopulation contributes cells not only to the pancreas and gall bladder but also to the liver. Cells equipped with a constellation of markers suggestive of the primitive endodermal phenotype exist in the peribiliary glands, the bile duct glands, of the intra- and extrahepatic bile ducts. These cells are able to be isolated and cultured easily, which demonstrates the persistence of a stable phenotype during in vitro expansion, the ability to self-renew in vitro, and the ability to differentiate between hepatocyte and biliary and pancreatic islet fates. In normal human livers, stem/progenitors cells are mostly restricted in two distinct niches, which are the bile ductules/canals of Hering and the peribiliary glands (PBGs) present inside the wall of large intrahepatic bile ducts. The existence of a network of stem/progenitor cell niches within the liver and along the entire biliary tree inform a patho-biological-based translational approach to biliary diseases and cholangiocarcinoma since it poses the basis to understand biliary regeneration after extensive or chronic injuries and progression to fibrosis and cancer.