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Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery
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Innate immunity in stem cell-derived hepatocytes.

Lena Fischer1, David C Hay2, Cliona O'Farrelly3

  • 1School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Republic of Ireland.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|May 23, 2018
PubMed
Summary
This summary is machine-generated.

Stem cell-derived hepatocyte-like cells (HLCs) exhibit innate immune responses, including interferon induction, similar to primary hepatocytes. However, HLCs show distinct differences in interferon-stimulated gene expression, making them valuable for modeling host-pathogen interactions.

Keywords:
hepatocytesinnate immunitystem cells

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Area of Science:

  • Cell Biology
  • Immunology
  • Regenerative Medicine

Background:

  • Hepatocyte-like cells (HLCs) derived from stem cells are promising for various applications, including disease modeling and tissue regeneration.
  • The innate immune system of hepatocytes is crucial for understanding host-pathogen interactions and graft survival, but its potential is still being uncovered.
  • Hepatocytes possess innate immune capabilities beyond their metabolic functions, involving pathogen detection and signaling pathways.

Purpose of the Study:

  • To review and compare the innate immune signaling pathways in HLCs with those in primary hepatocytes.
  • To highlight the potential of HLCs as a model system for studying host-pathogen interactions and immune responses in the liver.
  • To assess the suitability of HLCs for applications requiring a functional innate immune system, such as hepatotoxicity testing and regenerative medicine.

Main Methods:

  • Review of existing literature on innate immune signaling in HLCs and primary hepatocytes.
  • Comparative analysis of interferon (IFN) induction, IFN-stimulated gene (ISG) expression, and tumor necrosis factor-alpha (TNF-α) signaling.
  • Examination of toll-like receptor (TLR) expression patterns in HLCs versus primary hepatocytes.

Main Results:

  • HLCs demonstrate pathogen detection leading to IFN induction, with a notable preference for type III IFN over type I IFN, mirroring primary hepatocytes.
  • HLCs exhibit lower interferon-stimulated gene (ISG) expression levels compared to primary hepatocytes, indicating a differential response to IFN.
  • Tumor necrosis factor-alpha (TNF-α) signaling appears functional in HLCs, and while TLR expression is reported in primary hepatocytes, it remains understudied in HLCs.

Conclusions:

  • HLCs possess significant innate immune potential, making them superior to hepatoma cell lines for cell-based modeling despite some immature features.
  • Understanding the nuances of innate immune signaling in HLCs, particularly their IFN response and TLR expression, is critical for optimizing their use in research and clinical applications.
  • HLCs represent a valuable tool for advancing studies in liver disease, viral infections, and regenerative therapies due to their retained immune functions.