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Liver Regeneration in Health and Disease

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Abstract

In a healthy liver, the rate of cell turnover is very low; nevertheless regeneration of acutely lost modest amounts of parenchymal tissue is rapidly accomplished by the proliferation of normally quiescent hepatocytes. Hepatocytes are “primed” to enter the cell cycle by a number of cytokines and microRNAs, while many growth factors are implicated in “driving” proliferation. However, most liver disease presents as either acute liver failure or more chronic forms of injury (e.g., alcoholic fatty liver disease [AFLD], viral hepatitis, metabolic liver disease) where iterative injury has induced a state of hepatocyte senescence, thus necessitating the activation and mobilization of a potential stem cell population located within the intrahepatic biliary tree. Activation of these bipotential hepatic progenitor cells (HPCs) from the canal of Hering seems crucial for patient survival after acute forms of massive liver damage, and we are now beginning to understand the niche requirements and molecular signals that govern their cell fate. In particular, a stereotypical niche composed of myofibroblasts, macrophages, and laminin accompanies HPC expansion, and Wnt and Notch signalings seem crucial for hepatocytic and cholangiocytic differentiation, respectively.

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Authors and Affiliations

  1. Department of Tumour Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK

    Malcolm R. Alison Ph.D., D.Sc.

  2. Department of Oncology and Molecular Imaging, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK

    Shahriar Islam M.B.B.S.

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  1. Malcolm R. Alison Ph.D., D.Sc.
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Correspondence to Malcolm R. Alison Ph.D., D.Sc. .

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  1. New York State Health Department Wadsworth Center, Albany, New York, USA

    Stewart Sell

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Alison, M.R., Islam, S. (2013). Liver Regeneration in Health and Disease. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-7696-2_22

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