Conclusion: We have isolated an epithelial cell population from primary mouse gallbladder with stem cell characteristics and found it to be unique, compared to IHBD cells. (HEPATOLOGY 2011) Understanding the resident stem cell populations of the biliary system has great importance for basic biology and biliary diseases. The biliary tree is divided into the intra- and extrahepatic biliary systems. The latter consists of the gallbladder, cystic duct, and the common bile duct.1 The biliary system CHIR-99021 concentration is a conduit for bile to be transported from the liver to the intestine. The gallbladder, in
turn, stores the bile and regulates its content and concentration, playing an important role in the digestive process.2, 3 Though there has been a lot of recent interest in the liver stem cell field,4 there is still a paucity of data regarding gallbladder stem cells. The biliary system, hepatocytes, and ventral pancreas develop from the ventral foregut endoderm.5, 6 Histological evidence suggesting that both intra- and extrahepatic systems originate from the hepatic diverticulum has led to the hypothesis that they see more descend from the same progenitor cell. However, the cell-intrinsic factors that result in their specification have heretofore been unclear. Recently, it has been shown that the progenitor cells that give rise to each system separate out during development.7 Using
a Pdx1-Cre mouse, Spence et al.7 demonstrated that hepatocytes and intrahepatic bile duct (IHBD) cells derive from Pdx1- cells, whereas the extrahepatic bile duct (EHBD) cells and ventral pancreas derive from Pdx1+ cells. Sox17 controls the specification medchemexpress of the EHBD and pancreatic cells.
Sox17 loss-of-function embryos exhibit gallbladder agenesis and the presence of ectopic pancreatic tissue in the extrahepatic bile duct. Conversely, Sox17 gain of function results in ectopic ductal tissue in the developing pancreas. In both cases, the intrahepatic system is not affected. It appears that the IHBD and EHBD cells descend from separate progenitor cells governed by separate transcriptional cascades. It is, therefore, possible that adult IHBD and EHBD cells could be distinct, as well. The aims of this study were to isolate and characterize stem cells from the adult mouse gallbladder and compare their phenotypic and expression profiles with IHBD cells. In addition to basic biology, an understanding of gallbladder stem cells would be vital to the study of gallbladder carcinoma, a rare, but poorly understood, malignancy8 and congenital diseases involving biliary dysmorphogenesis, such as biliary atresia.9 It would also elucidate the ontogeny of cells in the biliary system. Stem cells are defined as undifferentiated cells that can self-renew at the single-cell level and form lineage-committed progeny.