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Cited by 208Liver physiology and pathologyLiver Diseases and ImmunityMesenchymal stem cell research

Characterisation of the liver progenitor cell niche in liver diseases: potential involvement of Wnt and Notch signalling

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Spee, Bart, Carpino, Guido, Schotanus, Baukje A, Katoonizadeh, Azeam, Borght, Sara Vander, Gaudio, Eugenio, Roskams, Tania·2010·Gut
DOI 10.1136/gut.2009.188367
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Abstract

Background Hepatic progenitor cells (HPCs) hold a great potential for therapeutic intervention for currently untreatable liver diseases. However, in human diseases molecular mechanisms involved in proliferation and differentiation of HPCs are poorly understood. Methods and results In the present study activated HPCs and their microenvironment (niche) were investigated in acute and chronic human liver disease by gene-expression analysis and immunohistochemistry/immunofluorescence. Cryopreserved liver tissues were used from patients with parenchymal versus biliary diseases: acute necrotising hepatitis (AH), cirrhosis after hepatitis C infection, and primary biliary cirrhosis in order to study differentiation of HPCs towards hepatocytic versus biliary lineage. Keratin 7 positive HPCs/reactive ductules were captured by means of laser capture microdissection and gene-expression profiles were obtained by using a customized PCR array. Gene expression results were confirmed by immunohistochemistry and immunofluorescence double staining. In all disease groups, microdissected HPCs expressed progenitor cell markers such as KRT7, KRT19, NCAM, ABCG2, LIF, KIT, OCT4, CD44 and TERT. In AH, HPCs were most activated and showed a high expression of prominin-1 (CD133) and alpha-fetoprotein, and a strong activation of the Wnt pathway. In contrast to parenchymal diseases, HPCs in primary biliary cirrhosis (biliary differentiation) showed a high activation of Notch signalling. Conclusion A distinc…

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  • The role of Notch signaling in post-resection liver regeneration is relatively limited, because liver mass restoration after resection is primarily driven by proliferation of residual hepatocytes rather than stem cell activation.

    “However, its role in post-resection LR is relatively limited, as liver mass restoration after resection is primarily driven by the proliferation of residual hepatocytes rather than stem cell activation[56].”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [56]

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Authors
Spee, B., Carpino, G., Schotanus, B. A., Katoonizadeh, A., Borght, S. V., Gaudio, E., & Roskams, T.
Affiliations
  • Universitair Ziekenhuis Leuven (BE)
  • Foro Italico University of Rome (IT)
  • Utrecht University (NL)
  • Sapienza University of Rome (IT)
Corresponding author
Spee, Bart
ORCID
Venue
Gut
Publisher
BMJ
Published
2009-11-01
Volume
59
Issue
2
Pages
247-257
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
DOI
10.1136/gut.2009.188367
OpenAlex
W2163623286
Cited by
208
References
2
Citations by year
2026: 1 · 2025: 8 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 9 · 2020: 12 · 2019: 9 · 2018: 14 · 2017: 12 · 2016: 18 · 2015: 18 · 2014: 20 · 2013: 24 · 2012: 17
FWCI
10.34
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Gut (publishedVersion)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
hepatic progenitor cells, Wnt signaling, Notch signaling, liver disease, hepatitis C cirrhosis, primary biliary cirrhosis, biliary differentiation, hepatocyte differentiation, CD133, alpha-fetoprotein, liver regeneration
MeSH terms
Acute Disease, Cell Differentiation, Chronic Disease, Humans, Liver Diseases, Stem Cells, Signal Transduction, Gene Expression Profiling, Hepatocytes, Microdissection, Cell Proliferation, Wnt Proteins, Receptors, Notch

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