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Abstract
There are currently no reports of identification of stem cells in human gallbladder. The differences between human gallbladder and intrahepatic bile duct (IHBD) cells have also not been explored. The goals of this study were to evaluate if human fetal gallbladder contains a candidate stem cell population and if fetal gallbladder cells are distinct from fetal IHBD cells. We found that EpCAM+CD44+CD13+ cells represent the cell population most enriched for clonal self-renewal from primary gallbladder. Primary EpCAM+CD44+CD13+ cells gave rise to EpCAM+CD44+CD13+ and EpCAM+CD44+CD13− cells in vitro, and gallbladder cells expanded in vitro exhibited short-term engraftment in vivo. Last, we found that CD13, CD227, CD66, CD26 and CD49b were differentially expressed between gallbladder and IHBD cells cultured in vitro indicating clear phenotypic differences between the two cell populations. Microarray analyses of expanded cultures confirmed that both cell types have unique transcriptional profiles with predicted functional differences in lipid, carbohydrate, nucleic acid and drug metabolism.In conclusion, we have isolated a distinct clonogenic population of epithelial cells from primary human fetal gallbladder with stem cell characteristics and found it to be unique compared to IHBD cells.
Highlights
Understanding the resident stem cell populations of the bile duct system is important for both basic biology and developing therapeutic strategies to treat bile duct diseases
These data were corroborated by a study in our lab, where we found that adult mouse gallbladder stem cells have a distinct phenotypic and expression profile compared to adult mouse intrahepatic bile duct (IHBD) cells [9]
EpCAM expression has been observed on adult human gallbladder epithelial cells [17, 18] but no evidence exists for its expression in fetal gallbladder
Summary
Understanding the resident stem cell populations of the bile duct system is important for both basic biology and developing therapeutic strategies to treat bile duct diseases. There is a paucity of data characterizing stem cells in both adult and fetal human gallbladders. Spence et al [8] by using a PDX1Cre transgenic mouse showed that hepatocytes and IHBD cells descend from Pdx1− cells while the EHBD cells including the ventral pancreas derive from Pdx1+ cells. These data were corroborated by a study in our lab, where we found that adult mouse gallbladder stem cells have a distinct phenotypic and expression profile compared to adult mouse IHBD cells [9]. The differences between human IHBD and EHBD cells have not yet been explored
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