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Cited by 187Liver physiology and pathologyDrug-Induced Hepatotoxicity and ProtectionTissue Engineering and Regenerative Medicine

Liver Regeneration in Rats with Retrorsine-Induced Hepatocellular Injury Proceeds through a Novel Cellular Response

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Gordon, Gavin J., Coleman, William B., Hixson, Douglas C., Grisham, Joe W.·2000·The American Journal of Pathology
DOI 10.1016/s0002-9440(10)64765-7PMC PMC1850042
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Abstract

The adult rodent liver contains at least two recognized populations of cells with stem-like properties that contribute to liver repair/regeneration under different pathophysiological circumstances: (i) unipotential committed progenitor cells (differentiated hepatocytes and biliary epithelial cells) and (ii) multipotential nonparenchymal progenitor cells (oval cells). In retrorsine-induced hepatocellular injury the capacity of fully differentiated rat hepatocytes to replicate is severely impaired and massive proliferation of oval cells does not occur. Nevertheless, retrorsine-exposed rats can replace their entire liver mass after 2/3 surgical partial hepatectomy through the emergence and expansion of a population of small hepatocyte-like progenitor cells that expresses phenotypic characteristics of fetal hepatoblasts, oval cells, and fully differentiated hepatocytes, but differ distinctly from each type of cell. The activation, proliferation, and complete regeneration of normal liver structure from small hepatocyte-like progenitor cells have not been recognized in other models of liver injury characterized by impaired hepatocyte replication. We suggest that the selective emergence and expansion of small hepatocyte-like progenitor cells observed in the retrorsine model reflect a novel mechanism of complete liver regeneration in the adult rat. Furthermore, we suggest that these cells may represent a novel progenitor cell population that (i) responds to liver deficit when the replication capacity of differentiated hepatocytes is impaired, (ii) expresses an extensive proliferative capacity, (iii) can give rise to large numbers of progeny hepatocytes, and (iv) can restore tissue mass.

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  • Small hepatocytes found in retrorsine-treated rat livers and small Thy1+ hepatocytes observed in rat livers following galactosamine-induced injury have robust regenerative properties.

    “An interesting but less well understood population of hepatocytes are the small hepatocytes found in retrorsine-treated rat livers[138], [139], [140] and the small Thy1+ hepatocytes observed in rat livers following galactosamine-induced injury141 (Fig. 3F). These small hepatocytes were reported to have robust regenerative properties.”

    From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [138]

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Cited by

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Authors
Gordon, G. J., Coleman, W. B., Hixson, D. C., & Grisham, J. W.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • Brown University (US)
Corresponding author
Coleman, William B.
ORCID
Coleman, William B.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2000-02
Volume
156
Issue
2
Pages
607-619
ISSN
0002-9440 (ISSN-L)
DOI
10.1016/s0002-9440(10)64765-7
PMC
PMC1850042
OpenAlex
W1995026118
Cited by
187
References
1
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 4 · 2014: 7 · 2013: 7 · 2012: 6
FWCI
8.77
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • National Institutes of Health
  • University of North Carolina at Chapel Hill
  • National Cancer Institute (CA29323, R01CA078434, CA78434)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
liver regeneration, retrorsine, hepatocyte injury, oval cells, hepatocyte proliferation, partial hepatectomy, liver repair
MeSH terms
Animals, Cell Line, Hepatectomy, Liver Diseases, Liver Regeneration, Male, Phenotype, Pyrrolizidine Alkaloids, Rats, Inbred F344, Stem Cells, Rats, Chemical and Drug Induced Liver Injury

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