Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?

Authors

  • Richard Kia,

    1. Department of Molecular and Clinical Pharmacology, University of Liverpool, MRC Centre for Drug Safety Science, Liverpool, UK
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    • These authors contributed equally
  • Rowena L. C. Sison,

    1. Department of Molecular and Clinical Pharmacology, University of Liverpool, MRC Centre for Drug Safety Science, Liverpool, UK
    2. Department of Molecular and Clinical Pharmacology, University of Liverpool, Stem Cells for Safer Medicine, Liverpool, UK
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    • These authors contributed equally
  • James Heslop,

    1. Department of Molecular and Clinical Pharmacology, University of Liverpool, MRC Centre for Drug Safety Science, Liverpool, UK
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    • These authors contributed equally
  • Neil R. Kitteringham,

    1. Department of Molecular and Clinical Pharmacology, University of Liverpool, MRC Centre for Drug Safety Science, Liverpool, UK
    2. Department of Molecular and Clinical Pharmacology, University of Liverpool, Stem Cells for Safer Medicine, Liverpool, UK
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  • Neil Hanley,

    1. Department of Molecular and Clinical Pharmacology, University of Liverpool, Stem Cells for Safer Medicine, Liverpool, UK
    2. Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
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  • John S. Mills,

    1. Science and Validation, Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, Cheshire, UK
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  • B. Kevin Park,

    1. Department of Molecular and Clinical Pharmacology, University of Liverpool, MRC Centre for Drug Safety Science, Liverpool, UK
    2. Department of Molecular and Clinical Pharmacology, University of Liverpool, Stem Cells for Safer Medicine, Liverpool, UK
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  • Chris E. P. Goldring

    Corresponding author
    1. Department of Molecular and Clinical Pharmacology, University of Liverpool, Stem Cells for Safer Medicine, Liverpool, UK
    • Department of Molecular and Clinical Pharmacology, University of Liverpool, MRC Centre for Drug Safety Science, Liverpool, UK
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Correspondence

Dr Chris Goldring, Department of Molecular and Clinical Pharmacology, University of Liverpool, MRC Centre for Drug Safety Science, Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK.

Tel.: +44 151 794 5979

Fax: +44 151 794 5540

E-mail: chrissy@liverpool.ac.uk

Abstract

Amongst the different types of adverse drug reactions, drug-induced liver injury is the most prominent cause of patient morbidity and mortality. However, the current available hepatic model systems developed for evaluating safety have limited utility and relevance as they do not fully recapitulate a fully functional hepatocyte, and do not sufficiently represent the genetic polymorphisms present in the population. The rapidly advancing research in stem cells raises the possibility of using human pluripotent stem cells in bridging this gap. The generation of human induced pluripotent stem cells via reprogramming of mature human somatic cells may also allow for disease modelling in vitro for the purposes of assessing drug safety and toxicology. This would also allow for better understanding of disease processes and thus facilitate in the potential identification of novel therapeutic targets. This review will focus on the current state of effort to derive hepatocytes from human pluripotent stem cells for potential use in hepatotoxicity evaluation and aims to provide an insight as to where the future of the field may lie.

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