Abstract

In normal human livers, EpCAMpos cells are mostly restricted in two distinct niches, which are (i) the bile ductules and (ii) the mucous glands present inside the wall of large intrahepatic bile ducts (the so-called peribiliary glands). These EpCAMpos cell niches have been proven to harbor stem/progenitor cells with great importance in liver and biliary tree regeneration and in the pathophysiology of human diseases. The EpCAMpos progenitor cells within bile ductules are engaged in driving regenerative processes in chronic diseases affecting hepatocytes or interlobular bile ducts. The EpCAMpos population within peribiliary glands is activated when regenerative needs are finalized to repair large intra- or extra-hepatic bile ducts affected by chronic pathologies, including primary sclerosing cholangitis and ischemia-induced cholangiopathies after orthotopic liver transplantation. Finally, the presence of distinct EpCAMpos cell populations may explain the histological and molecular heterogeneity characterizing cholangiocarcinoma, based on the concept of multiple candidate cells of origin. This review aimed to describe the precise anatomical distribution of EpCAMpos populations within the liver and the biliary tree and to discuss their contribution in the pathophysiology of human liver diseases, as well as their potential role in regenerative medicine of the liver.

Highlights

  • In the adult liver and biliary tree, mature parenchymal cells are characterized by remarkable proliferative capabilities, which support the regenerative needs of these organs in physiological conditions [1]

  • The liver and the biliary tree harbor two EpCAMpos stem/progenitor cell niches, both yielding high regenerative capabilities and the potential to differentiate into mature hepatocytes and cholangiocytes, but displaying distinct localization and phenotype and peculiar behavior and role in the physio-pathogenesis of liver and biliary diseases

  • EpCAMpos hepatic stem/progenitor cell (HpSC) are located at the canals of Hering and in the bile ductules; these cells are recruited in human acute and chronic liver diseases affecting hepatocytes, contributing to liver regeneration and being implicated in the fibrogenetic processes

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Summary

Frontiers in Medicine

EpCAMpos cells are mostly restricted in two distinct niches, which are (i) the bile ductules and (ii) the mucous glands present inside the wall of large intrahepatic bile ducts (the so-called peribiliary glands). These EpCAMpos cell niches have been proven to harbor stem/progenitor cells with great importance in liver and biliary tree regeneration and in the pathophysiology of human diseases. The EpCAMpos population within peribiliary glands is activated when regenerative needs are finalized to repair large intra- or extra-hepatic bile ducts affected by chronic pathologies, including primary sclerosing cholangitis and ischemia-induced cholangiopathies after orthotopic liver transplantation.

INTRODUCTION
THE HETEROGENEITY OF EPCAMPOS CELL POPULATIONS IN HUMAN LIVER
EpCAMpos Cells Within PBGs in Human Cholangiopathies
EPCAMPOS CELL POPULATIONS IN CHOLANGIOCARCINOMA
PERSPECTIVES AND APPLICATIONS OF EPCAMPOS CELLS IN REGENERATIVE MEDICINE
CONCLUSION
AUTHOR CONTRIBUTIONS
Full Text
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