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Cited by 177Liver physiology and pathologyMesenchymal stem cell researchLiver Diseases and Immunity

Epithelial Cell Adhesion Molecule (EpCAM) Marks Hepatocytes Newly Derived from Stem/Progenitor Cells in Humans Δσ

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Yoon, So-Mi, Gerasimidou, Domniki, Kuwahara, Reiichiro, Hytiroglou, Prodromos, Yoo, Jeong Eun, Park, Young Nyun, Theise, Neil D.·2011·Hepatology
DOI 10.1002/hep.24122
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Abstract

Epithelial cell adhesion molecule (EpCAM) is a surface marker on human hepatic stem/progenitor cells that is reported as absent on mature hepatocytes. However, it has also been noted that in cirrhotic livers of diverse causes, many hepatocytes have EpCAM surface expression; this may represent aberrant EpCAM expression in injured hepatocytes or, as we now hypothesize, persistence of EpCAM in hepatocytes that have recently derived from hepatobiliary progenitors. To evaluate this concept, we investigated patterns of EpCAM expression in hepatobiliary cell compartments of liver biopsy specimens from patients with all stages of chronic hepatitis B and C, studying proliferation, senescence and telomere lengths. We found that EpCAM(+) hepatocytes were rare in early stages of disease, became increasingly prominent in later stages in parallel with the emergence of ductular reactions, and were consistently arrayed around the periphery of cords of keratin 19(+) hepatobiliary cells of the ductular reaction, with which they shared EpCAM expression. Proliferating cell nuclear antigen (proliferation marker) and p21 (senescence marker) were both higher in hepatocytes in cirrhosis than in normal livers, but ductular reaction hepatobiliary cells had the highest proliferation rate, in keeping with being stem/progenitor cell–derived transit amplifying cells. Telomere lengths in EpCAM(+) hepatocytes in cirrhosis were higher than EpCAM(−) hepatocytes ( P < 0.046), and relatively shorter than those in the corresponding ductular reaction hepatobiliary cells ( P = 0.057). Conclusion: These morphologic, topographic, immunophenotypic, and molecular data support the concept that EpCAM(+) hepatocytes in chronic viral hepatitis are recent progeny of the hepatobiliary stem/progenitor cell compartment through intermediates of the transit amplifying, ductular reaction hepatobiliary cells. (Hepatology 2011)

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  • In chronic liver diseases, HHs with expression of progenitor-associated markers were documented in regenerative nodules.

    “Notably, in chronic liver diseases, HHs with expression of progenitor-associated markers were also documented in regenerative nodules (Michalopoulos and Khan, 2015; Yoon et al., 2011”

    From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Yoon et al., 2011

    The Results report EpCAM-positive hepatocytes in chronic hepatitis, with staining more extensive in cirrhotic livers; the paper identifies EpCAM as a hepatic stem/progenitor-cell marker. It does not identify those cells as HHs or specifically document their location within regenerative nodules. Its Discussion mentions regenerative nodules when reporting a separate study by Lin et al. (LLM, conf=0.82)

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Research works printed but not linked: 28

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Authors
Yoon, S.-M., Gerasimidou, D., Kuwahara, R., Hytiroglou, P., Yoo, J. E., Park, Y. N., & Theise, N. D.
Affiliations
  • Yonsei University (KR)
  • Aristotle University of Thessaloniki (GR)
  • Kurume University (JP)
  • Mount Sinai Beth Israel (US)
Corresponding author
  • Park, Young Nyun
  • Theise, Neil D.
ORCID
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-03
Volume
53
Issue
3
Pages
964-973
ISSN
0270-9139 (ISSN-L)
DOI
10.1002/hep.24122
OpenAlex
W2061644566
Cited by
177
References
0
Citations by year
2026: 2 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 5 · 2021: 5 · 2020: 10 · 2019: 12 · 2018: 10 · 2017: 17 · 2016: 15 · 2015: 13 · 2014: 20 · 2013: 15 · 2012: 23
FWCI
9.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders
  • Korea Science and Engineering Foundation
  • Japan Society for the Promotion of Science (23790823)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
EpCAM, hepatocytes, liver progenitor cells, ductular reaction, liver cirrhosis, chronic hepatitis B, chronic hepatitis C, telomere length, cellular senescence, p21, transit amplifying cells, keratin 19, hepatocyte proliferation
MeSH terms
Epithelial Cell Adhesion Molecule, Antigens, Neoplasm, Humans, Liver, Liver Cirrhosis, Stem Cells, Cell Adhesion Molecules, Telomere, Cellular Senescence, Hepatitis B, Chronic, Hepatitis C, Chronic, Hepatocytes, Cell Proliferation

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