Gallbladder as a novel source of stem cells of the hepatobiliary system

Abstract

BackgroundThe identification and characterization of stem cells within the biliary system has great importance for basic biology and potential cell‐based therapy. Currently, there is a paucity of data regarding stem cells in the gallbladder. Recent data have shown that the intra‐hepatic and extra‐hepatic biliary systems develop from separate progenitors. Therefore, in the adult hepatobiliary system extra‐hepatic stem cells would be unique compared to intra‐hepatic bile duct stem cells.AimTo isolate and characterize stem cells from the adult mouse gallbladder and determine their uniqueness relative to intra‐hepatic bile duct (IHBD) cells.MethodsGallbladder cells were expanded in vitro on feeders. Limiting Dilution Analyses and Index sorts were performed to evaluate candidate stem cells markers. A matrigel‐based assay was used to examine lineage commitment of the gallbladder cells.ConclusionsWe identify CD49f as a gallbladder stem cell marker. Gallbladder stem cells exhibit clonogenic self‐renewal and morphogenesis in vitro, expand and form structures in vivo short term. Primary gallbladder and IHBD cells exhibit different phenotypic profiles by flow cytometry. Microarray analyses on gallbladder stem cells and IHBD cells in vitro indicate different genomic expression patterns. These data underscore the uniqueness of gallbladder stem cells.This work was in part supported by the Commonwealth of Pennsylvania and by the NIH grant R01 DK085711.