For now, check details these data conclusively show that parent and clonal EpCAM+CD49f+ cells can organize into organotypic structures that mimic the morphology, ultrastructure, and function of the native gallbladder, both invitro and invivo. Spence et al.7 have recently showed that IHBD cells and EHBD cells develop from separate precursors. However, there are no reports describing their similarities or differences in the adult. We found that expression of CD49f, CD49e, CD81, CD26, CD54, and CD166 was different between primary IHBD cells and gallbladder cells. The aim of our experiment was to evaluate the differences,

if any, between gallbladder stem cells and IHBD cells. Expanded EpCAM+CD49f+ gallbladder cells (>p0) represent a purer stem cell population than primary EpCAM+CD49fhi cells. The latter forms both flat and glandular colonies, and only a fraction of the flat see more colonies can self-renew. Therefore, we ran microarray analyses on expanded EpCAM+CD49f+ cells (>p1) and expanded IHBD cells. The major groups of differentially expressed genes were CYP genes, GST, and the solute carrier family genes. Also, interferon (IFN)-inducible protein 27 was differentially expressed between gallbladder cells and IHBD cells. Interestingly, the expression of CD54 is known to be

immunologically mediated.36 The immunologic properties of bile duct cells have long been considered. They are MCE the primary site of damage in inflammatory diseases, such as primary biliary cirrhosis37 and biliary atresia9 and in liver allograft rejection.38 The differential expression of an IFN-inducible protein and CD54 indicates that the immunologic properties of IHBD cells and gallbladder cells could be different. Studies of IHBD cells are hindered by a technical inability to isolate and expand them from primary tissue.2, 39 We circumvented this hurdle by using LA7 feeder cells that allow for a robust expansion of IHBD epithelial (EpCAM+) cells.

This expansion assay, along with the 3D Matrigel assay, could serve as interchangeable, technically easy tools to study bile duct cells. In all, the complete elucidation of the differences between IHBD cells and gallbladder cells belongs to another study, as does the evaluation of the stem cell characteristics of expanded IHBD cells. The focus of this article was to isolate and characterize gallbladder stem cells. We postulate that this study will have important clinical significance. Gallbladder stem cells could be used to treat biliary atresia, as has been noted with hepatic progenitor cells.40 These cells could also be reprogrammed into hepatocytes or endocrine cells. There have been recent reports of the differentiation of gallbladder epithelial cells into hepatocytes,34, 41 and ectopic endocrine cells have been observed in the EHBD cells of Hes1−/− deficient mice.