Current Pathobiology Reports

, Volume 5, Issue 3, pp 301–314 | Cite as

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)
First Online:
Part of the following topical collections:
  1. Application of Stem Cells in Endoderm Derivatives

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.

Keywords

Human pluripotent stem cells Induced pluripotent stem cells Embryonic stem cells Endoderm Hepatocytes Hepatic differentiation 
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Notes

Acknowledgements

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

Compliance with Ethical Standards

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.

Human and Animal Rights and Informed Consent

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

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Richard Siller
    • 1
    • 2
  • Sebastian Greenhough
    • 1
  • Santosh Mathapati
    • 1
    • 2
  • Karim Si-Tayeb
    • 3
    • 4
    • 5
    • 6
  • Gareth J. Sullivan
    • 1
    • 2
    • 7
    • 8
  1. 1.Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of MedicineUniversity of OsloOsloNorway
  2. 2.Norwegian Center for Stem Cell ResearchOsloNorway
  3. 3.CNRS, UMR 6291NantesFrance
  4. 4.Université de NantesNantesFrance
  5. 5.CHU Nantes, L’institut du thorax, CIC Endocrinology-NutritionNantesFrance
  6. 6.INSERM, UMR1087, L’institut du thoraxNantesFrance
  7. 7.Institute of ImmunologyOslo University Hospital-RikshospitaletOsloNorway
  8. 8.Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical SciencesUniversity of OsloOsloNorway

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