AI Article Synopsis
- Human gallbladders harbor multipotent stem/progenitor cells located in mucosal crypts, instead of peribiliary glands, and can be identified using EpCAM.
- Most isolated EpCAM+ cells exhibit stemness characteristics and can easily be cultured, demonstrating the ability to differentiate into various mature cell types related to liver and pancreatic functions.
- Transplantation of these EpCAM+ cells into immune-compromised mice leads to the successful generation of human liver cells, suggesting potential therapeutic applications in liver diseases like cirrhosis.
Article Abstract
Background & Aims: Multipotent stem/progenitor cells are found in peribiliary glands throughout human biliary trees and are able to generate mature cells of hepato-biliary and pancreatic endocrine lineages. The presence of endodermal stem/progenitors in human gallbladder was explored.
Methods: Gallbladders were obtained from organ donors and laparoscopic surgery for symptomatic cholelithiasis. Tissues or isolated cells were characterized by immunohistochemistry and flow cytometry. EpCAM+ (Epithelial Cell Adhesion Molecule) cells were immunoselected by magnetic microbeads, plated onto plastic in self-replication conditions and subsequently transferred to distinct serum-free, hormonally defined media tailored for differentiation to specific adult fates. In vivo studies were conducted in an experimental model of liver cirrhosis.
Results: The gallbladder does not have peribiliary glands, but it has stem/progenitors organized instead in mucosal crypts. Most of these can be isolated by immune-selection for EpCAM. Approximately 10% of EpCAM+ cells in situ and of immunoselected EpCAM+ cells co-expressed multiple pluripotency genes and various stem cell markers; other EpCAM+ cells qualified as progenitors. Single EpCAM+ cells demonstrated clonogenic expansion ex vivo with maintenance of stemness in self-replication conditions. Freshly isolated or cultured EpCAM+ cells could be differentiated to multiple, distinct adult fates: cords of albumin-secreting hepatocytes, branching ducts of secretin receptor+ cholangiocytes, or glucose-responsive, insulin/glucagon-secreting neoislets. EpCAM+ cells transplanted in vivo in immune-compromised hosts gave rise to human albumin-producing hepatocytes and to human Cytokeratin7+ cholangiocytes occurring in higher numbers when transplanted in cirrhotic mice.
Conclusions: Human gallbladders contain easily isolatable cells with phenotypic and biological properties of multipotent, endodermal stem cells.
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| http://dx.doi.org/10.1016/j.jhep.2014.01.026 | DOI Listing |
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