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Biology of Human Liver Stem Cells

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Stem Cells Handbook

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Abstract

Although until recently the existence of the liver stem cell was questioned, now the race is on to obtain and characterize the human liver stem cell for clinical therapeutic use for gene replacement, liver repopulation, drug development, and bioartificial liver support systems. Experimental models have identified cells at different stages in the hepatocyte lineage, including mature hepatocytes, bipotential ductular cells (so-called oval cells), as well as blood-derived periductular cells, as possible liver progenitor cells (LPCs). In the human liver, many cholestatic diseases, associated with loss of bile ducts and proliferation of “ductular proliferative cells” with an appearance similar to oval cells, are seen. The origin of these cells is not clear; possibilities considered are canals of Hering, mature bile duct cells, metaplasia of hepatocytes, and blood-borne stem cells that locate in the liver. Specific markers for these cells have not been identified, but OV-6, a marker identified by a monoclonal antibody to a cytokeratin in rat oval cells and bile ducts, has been shown to identify a presumptive human LPC. Other markers seen on human oval cells are CD34 and c-kit, markers shared by hematopoietic stem cells, and indeed, after bone marrow transplantation, donor cells can be found in the recipient liver, albeit rarely. Cells from injured or normal human liver expressing c-kit have been selected, cultured in vitro, and shown to express biliary phenotype; cells expressing CD34 have been shown to give rise to hepatic epithelial cell phenotype; and cells expressing endothelial phenotype have also been identified. In addition, a CD34-, c-kit - mesenchymal cell from the bone marrow (so-called multipotential adult progenitor cell) can differentiate into hepatocytes. Human fetal hepatoblasts may also serve as a source for LPCs. A number of different factors may control differentiation of liver precursor cells, including Jagged/Notch signaling. Much further work is required before the potential of the therapeutic use of liver stem cells can be realized.

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Authors
  1. Alastair J. Strain PhD
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  2. Sarbjit S. Nijjar PhD
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  3. Heather A. Crosby PhD
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  1. Wadsworth Center and Ordway Research Institute, Empire State Plaza, Albany, NY, USA

    Stewart Sell MD

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Strain, A.J., Nijjar, S.S., Crosby, H.A. (2004). Biology of Human Liver Stem Cells. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-411-5_35

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  • DOI: https://doi.org/10.1007/978-1-59259-411-5_35

  • Publisher Name: Humana Press, Totowa, NJ

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