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Future Challenges in the Generation of Hepatocyte-Like Cells From Human Pluripotent Stem Cells

  • Application of Stem Cells in Endoderm Derivatives (K Si-Tayeb and G Sullivan, Section Editors)
  • Published:
Current Pathobiology Reports

Abstract

Purpose of Review

The purpose of this review is to provide an updated perspective on directing human pluripotent stem cells (hPSCs) to hepatocyte-like-cells (HLCs) and the associated challenges.

Recent Findings

Recent advances in the hepatocyte differentiation field have largely been focused on increasing the reproducibility and definition of culture systems to further their translation to a clinical setting. There have been advances using new extracellular matrices such as human laminins, and recent work using small molecules to drive the differentiation process has dramatically reduced the cost of producing HLCs with equivalent phenotypes to growth factor-derived cells.

Summary

There are still several key aspects that remain unresolved, including the immature phenotype of hPSC-derived HLCs (a major hurdle for hPSC-derived progeny). Another key question is the zonal identity of the HLCs produced in vitro, which will have major implications in terms of disease modeling and drug metabolism. To date, there has been little investigation of this aspect of hepatic biology reported in the field.

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Acknowledgements

The authors would like to thank Carina Knudsen at the University of Oslo Photo and Graphics Service for the illustration in Fig. 1.

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Author notes

  1. Richard Siller and Sebastian Greenhough contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, PO Box 1112, Blindern, 0317, Oslo, Norway

    Richard Siller, Sebastian Greenhough, Santosh Mathapati & Gareth J. Sullivan

  2. Norwegian Center for Stem Cell Research, PO Box 1112, Blindern, 0317, Oslo, Norway

    Richard Siller, Santosh Mathapati & Gareth J. Sullivan

  3. CNRS, UMR 6291, 44000, Nantes, France

    Karim Si-Tayeb

  4. Université de Nantes, 44000, Nantes, France

    Karim Si-Tayeb

  5. CHU Nantes, L’institut du thorax, CIC Endocrinology-Nutrition, 44000, Nantes, France

    Karim Si-Tayeb

  6. INSERM, UMR1087, L’institut du thorax, 44000, Nantes, France

    Karim Si-Tayeb

  7. Institute of Immunology, Oslo University Hospital-Rikshospitalet, PO Box 4950, Nydalen, 0424, Oslo, Norway

    Gareth J. Sullivan

  8. Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, Blindern, Oslo, Norway

    Gareth J. Sullivan

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  1. Richard Siller
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Correspondence to Karim Si-Tayeb or Gareth J. Sullivan.

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Conflict of Interest

Richard Siller, Santosh Mathapati, and Karim Si-Tayeb declare that they have no conflict of interest.

Gareth J Sullivan is named as an inventor on a provisional application for a patent describing the small molecule-driven hepatocyte differentiation of human pluripotent stem cells.

Sebastian Greenhough is named as an inventor on a provisional application for a patent describing the small molecule-driven hepatocyte differentiation of human pluripotent stem cells.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Application of Stem Cells in Endoderm Derivatives

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Siller, R., Greenhough, S., Mathapati, S. et al. Future Challenges in the Generation of Hepatocyte-Like Cells From Human Pluripotent Stem Cells. Curr Pathobiol Rep 5, 301–314 (2017). https://doi.org/10.1007/s40139-017-0150-x

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