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Cited by 410Liver physiology and pathologyMesenchymal stem cell researchOrgan Transplantation Techniques and Outcomes

The origin and liver repopulating capacity of murine oval cells

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Wang, Xin, Foster, Mark, Al-Dhalimy, Muhsen, Lagasse, Eric, Finegold, Milton, Grompe, Markus·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1734199100PMC PMC304102
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Abstract

The appearance of bipotential oval cells in chronic liver injury suggests the existence of hepatocyte progenitor/stem cells. To study the origin and properties of this cell population, oval cell proliferation was induced in adult mouse liver by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and a method for their isolation was developed. Transplantation into fumarylacetoacetate hydrolase (Fah) deficient mice was used to determine their capacity for liver repopulation. In competitive repopulation experiments, hepatic oval cells were at least as efficient as mature hepatocytes in repopulating the liver. In mice with chimeric livers, the oval cells were not derived from hepatocytes but from liver nonparenchymal cells. This finding supports a model in which intrahepatic progenitors differentiate into hepatocytes irreversibly. To determine whether oval cells originated from stem cells residing in the bone marrow, bone marrow transplanted wild-type mice were treated with DDC for 8 months and oval cells were then serially transferred into Fah mutants. The liver repopulating cells in these secondary transplant recipients lacked the genetic markers of the original bone marrow donor. We conclude that hepatic oval cells do not originate in bone marrow but in the liver itself, and that they have valuable properties for therapeutic liver repopulation.

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  • Recent studies have demonstrated that HPCs arise within the liver, engraft the parenchyma, and may have some differentiation capacity but did not regenerate significant quantities of liver parenchyma.

    “These studies demonstrated that HPCs arise within the liver, engraft the parenchyma14 and may have some differentiation capacity but did not regenerate significant quantities of liver parenchyma11-13.”

    From Hepatic progenitor cells of biliary origin with liver repopulation capacity (2015) · cites this paper as [14]

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Authors
Wang, X., Foster, M., Al-Dhalimy, M., Lagasse, E., Finegold, M., & Grompe, M.
Affiliations
Oregon Health & Science University (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-09-30
Volume
100
Issue
suppl_1
Pages
11881-11888
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1734199100
PMC
PMC304102
OpenAlex
W1998666537
Cited by
410
References
51
Citations by year
2025: 3 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 8 · 2019: 7 · 2018: 10 · 2017: 12 · 2016: 11 · 2015: 26 · 2014: 22 · 2013: 27 · 2012: 28
FWCI
16.59
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK048252, R01-DK48252)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
oval cells, hepatic progenitor cells, liver repopulation, cell of origin, fumarylacetoacetate hydrolase deficiency, bone marrow transplantation, liver regeneration, chronic liver injury, non-parenchymal liver cells
MeSH terms
Animals, Base Sequence, Cell Differentiation, Dicarbethoxydihydrocollidine, DNA, Hydrolases, Liver, Mice, Transgenic, Models, Biological, Proteins, Mice, Knockout, Tyrosinemias, RNA, Untranslated, Hepatocytes, Multipotent Stem Cells, Mice

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