The stem cell niche of human livers: Symmetry between development and regeneration

Authors

  • Lili Zhang,

    1. Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC
    2. Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
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    • These authors contributed equally to this work.

  • Neil Theise,

    1. Departments of Pathology and of Medicine (Division of Digestive Diseases), Beth Israel Medical Center of Albert Einstein College of Medicine, New York, NY
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    • These authors contributed equally to this work.

  • Michael Chua,

    1. Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC
    2. Michael Hooker Microscopy Facility, University of North Carolina School of Medicine, Chapel Hill, NC
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  • Lola M. Reid

    Corresponding author
    1. Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC
    2. Department of Biomedical Engineering, University of North Carolina School of Medicine, Chapel Hill, NC
    3. Program in Molecular Biology and Biotechnology, Cancer Center, and Center for Gastrointestinal and Biliary Disease Biology, University of North Carolina School of Medicine, Chapel Hill, NC
    • Department of Cell and Molecular Physiology, CB# 7038, UNC School of Medicine, Chapel Hill, NC 27599
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    • fax: 919-966-6112.


  • Potential conflict of interest: Nothing to report.

Abstract

Human livers contain two pluripotent progenitors: hepatic stem cells and hepatoblasts. The hepatic stem cells uniquely express the combination of epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), cytokeratin (CK) 19, albumin ±, and are negative for α-fetoprotein (AFP). They are precursors to hepatoblasts, which differ from hepatic stem cells in size, morphology, and in expressing the combination of EpCAM, intercellular cell adhesion molecule (ICAM-1), CK19, albumin++, and AFP++. The hepatic stem cells are located in vivo in stem cell niches: the ductal plates in fetal and neonatal livers and canals of Hering in pediatric and adult livers. The hepatoblasts are contiguous to the niches, decline in numbers with age, wax and wane in numbers with injury responses, and are proposed to be the liver's transit-amplifying cells. In adult livers, intermediates between hepatic stem cells and hepatoblasts and between hepatoblasts and adult parenchyma are observed. Amplification of one or both pluripotent cell subpopulations can occur in diseases; for example, hepatic stem cell amplification occurs in mild forms of liver failure, and hepatoblast amplification occurs in forms of cirrhosis. Liver is, therefore, similar to other tissues in that regenerative processes in postnatal tissues parallel those occurring in development and involve populations of stem cells and progenitor cells that can be identified by anatomic, antigenic, and biochemical profiles. (HEPATOLOGY 2008;48:1598–1607.)

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