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.
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http://dx.doi.org/10.1016/j.scr.2014.12.003 | DOI Listing |
Liver Int
February 2024
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Background & Aims: Alagille syndrome (ALGS) manifests with peripheral intrahepatic bile duct (IHBD) paucity, which can spontaneously resolve. In a model for ALGS, Jag1 mice, this occurs with distinct architectural mechanisms in hilar and peripheral IHBDs. Here, we investigated region-specific IHBD characteristics and addressed whether IGF1, a cholangiocyte mitogen that is downregulated in ALGS and in Jag1 mice, can improve biliary outcomes.
View Article and Find Full Text PDFAm J Pathol
October 2023
Division of Digestive Diseases, Department of Medicine, Emory University, Atlanta, Georgia; Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, Georgia. Electronic address:
In the liver, biliary epithelial cells (BECs) line intrahepatic bile ducts (IHBDs) and are primarily responsible for modifying and transporting hepatocyte-produced bile to the digestive tract. BECs comprise only 3% to 5% of the liver by cell number but are critical for maintaining choleresis through homeostasis and disease. To this end, BECs drive an extensive morphologic remodeling of the IHBD network termed ductular reaction (DR) in response to direct injury or injury to the hepatic parenchyma.
View Article and Find Full Text PDFCell Stem Cell
May 2022
Erasmus MC Transplant Institute, University Medical Center Rotterdam, Department of Surgery, Rotterdam, the Netherlands. Electronic address:
Human cholangiocyte organoids show great promise for regenerative therapies and in vitro modeling of bile duct development and diseases. However, the cystic organoids lack the branching morphology of intrahepatic bile ducts (IHBDs). Here, we report establishing human branching cholangiocyte organoid (BRCO) cultures.
View Article and Find Full Text PDFWorld J Hepatol
February 2022
Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan.
Background: The role of the hepatic nervous system in liver development remains unclear. We previously created functional human micro-hepatic tissue in mice by co-culturing human hepatic endodermal cells with endothelial and mesenchymal cells. However, they lacked Glisson's sheath [the portal tract (PT)].
View Article and Find Full Text PDFClin Transl Med
December 2021
Erasmus MC, Department of Surgery, University Medical Center Rotterdam, Rotterdam, The Netherlands.
The well-established 3D organoid culture method enabled efficient expansion of cholangiocyte-like cells from intrahepatic (IHBD) and extrahepatic bile duct (EHBD) tissue biopsies. The extensive expansion capacity of these organoids enables various applications, from cholangiocyte disease modelling to bile duct tissue engineering. Recent research demonstrated the feasibility of culturing cholangiocyte organoids from bile, which was minimal-invasive collected via endoscopic retrograde pancreaticography (ERCP).
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