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Cell Biology and Toxicology, Volume 32, Issue 5, pp 403–417 | Cite as

Chemically induced hepatotoxicity in human stem cell-induced hepatocytes compared with primary hepatocytes and HepG2

  • Seok-Jin Kang
  • Hyuk-Mi Lee
  • Young-Il Park
  • Hee Yi
  • Hunjoo Lee
  • ByungJae So
  • Jae-Young Song
  • Hwan-Goo KangEmail author
Original Article

Abstract

Stem cell-induced hepatocytes (SC-iHeps) have been suggested as a valuable model for evaluating drug toxicology. Here, human-induced pluripotent stem cells (QIA7) and embryonic stem cells (WA01) were differentiated into hepatocytes, and the hepatotoxic effects of acetaminophen (AAP) and aflatoxin B1 (AFB1) were compared with primary hepatocytes (p-Heps) and HepG2. In a cytotoxicity assay, the IC50 of SC-iHeps was similar to that in p-Heps and HepG2 in the AAP groups but different from that in p-Heps of the AFB1 groups. In a multi-parameter assay, phenotypic changes in mitochondrial membrane potential, calcium influx and oxidative stress were similar between QIA7-iHeps and p-Heps following AAP and AFB1 treatment but relatively low in WA01-iHeps and HepG2. Most hepatic functional markers (hepatocyte-specific genes, albumin/urea secretion, and the CYP450 enzyme activity) were decreased in a dose-dependent manner following AAP and AFB1 treatment in SC-iHeps and p-Heps but not in HepG2. Regarding CYP450 inhibition, the cell viability of SC-iHeps and p-Heps was increased by ketoconazole, a CYP3A4 inhibitor. Collectively, SC-iHeps and p-Heps showed similar cytotoxicity and hepatocyte functional effects for AAP and AFB1 compared with HepG2. Therefore, SC-iHeps have phenotypic characteristics and sensitivity to cytotoxic chemicals that are more similar to p-Heps than to HepG2 cells.

Keywords

Hepatotoxicity Stem cell-induced hepatocyte Primary hepatocyte HepG2 

Notes

Acknowledgments

This project was supported by research funds from Animal and Plant Quarantine Agency (QIA), Republic of Korea.

Compliance with ethical standards

The experiments were approved by the ethics committee of QIA, Republic of Korea.

Supplementary material

10565_2016_9342_MOESM1_ESM.doc (30 kb)
ESM 1 (DOC 29 kb)
10565_2016_9342_MOESM2_ESM.doc (46 kb)
ESM 2 (DOC 46 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Seok-Jin Kang
    • 1
  • Hyuk-Mi Lee
    • 1
  • Young-Il Park
    • 1
  • Hee Yi
    • 1
  • Hunjoo Lee
    • 2
  • ByungJae So
    • 1
  • Jae-Young Song
    • 1
  • Hwan-Goo Kang
    • 1
    Email author
  1. 1.Veterinary Drugs and Biologics DivisionAnimal and Plant Quarantine AgencyAnyangRepublic of Korea
  2. 2.CHEM.I.NET LtdSeoulRepublic of Korea

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