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Scientific article
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English

Pharmacological Induction of a Progenitor State for the Efficient Expansion of Primary Human Hepatocytes

Published inHepatology, vol. 69, no. 5, p. 2214-2231
Publication date2019
Abstract

The liver is an organ with strong regenerative capacity, yet primary hepatocytes have a low amplification potential in vitro, a major limitation for the cell-based therapy of liver disorders and for ex vivo biological screens. Induced pluripotent stem cells (iPSCs) may help to circumvent this obstacle but often harbor genetic and epigenetic abnormalities, limiting their potential. Here, we describe the pharmacological induction of proliferative human hepatic progenitor cells (HPCs) through a cocktail of growth factors and small molecules mimicking the signaling events involved in liver regeneration. Human HPCs from healthy donors and pediatric patients proliferated vigorously while maintaining their genomic stability and could be redifferentiated in vitro into metabolically competent cells that supported the replication of hepatitis B and delta viruses. Redifferentiation efficiency was boosted by three-dimensional culture. Finally, transcriptome analysis showed that HPCs were more closely related to mature hepatocytes than iPSC-derived hepatocyte-like cells were. Conclusion: HPC induction holds promise for a variety of applications such as ex vivo disease modeling, personalized drug testing or metabolic studies, and development of a bioartificial liver.

Funding
  • Autre - ERC‐2010‐AdG‐268721‐KRABnKAP et ERC‐2008‐AdG‐233130‐HEPCENT
  • European Commission - POTENTIAL OF INDUCED PLURIPOTENT STEM CELLS FOR THE TREATMENT OF CRIGLER-NAJJAR LIVER DISEASE: A PRECLINICAL SAFETY ASSESSMENT [625689]
Citation (ISO format)
UNZU, Carmen et al. Pharmacological Induction of a Progenitor State for the Efficient Expansion of Primary Human Hepatocytes. In: Hepatology, 2019, vol. 69, n° 5, p. 2214–2231. doi: 10.1002/hep.30425
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ISSN of the journal0270-9139
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Creation11/12/2019 8:52:00 AM
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