his.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Drug metabolizing enzyme and transporter protein profiles of hepatocytes derived from human embryonic and induced pluripotent stem cells
AstraZeneca, Sweden / Cellectis AB, Sweden / University of Oslo, Norway.
AstraZeneca, Sweden.
Cellectis AB, Sweden.
Cellectis AB, Sweden.
Show others and affiliations
2013 (English)In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 86, no 5, 691-702 p.Article in journal (Refereed) Published
Abstract [en]

Human embryonic and induced pluripotent stem cell-derived hepatocytes (hESC-Hep and hiPSC-Hep) have the potential to provide relevant human in vitro model systems for toxicity testing and drug discovery studies. In this study, the expression and function of important drug metabolizing cytochrome P450 (CYP) enzymes and transporter proteins in hESC-Hep and hiPSC-Hep were compared to cryopreserved human primary hepatocytes (hphep) and HepG2 cells. Overall, CYP activities in hESC-Hep and hiPSC-Hep were much lower than in hphep cultured for 4 h, but CYP1A and 3A activities were comparable to levels in hphep cultured for 48 h (CYP1A: 35% and 26% of 48 h hphep, respectively; CYP3A: 80% and 440% of 48 h hphep, respectively). Importantly, in hESC-Hep and hiPSC-Hep, CYP activities were stable or increasing for at least one week in culture which was in contrast to the rapid loss of CYP activities in cultured hphep between 4 and 48 h after plating. With regard to transporters, in hESC-Hep and hiPSC-Hep, pronounced NTCP activity (17% and 29% of 4 h hphep, respectively) and moderate BSEP activity (6% and 8% of 4 h hphep, respectively) were observed. Analyses of mRNA expression and immunocytochemistry supported the observed CYP and transporter activities and showed expression of additional CYPs and transporters. In conclusion, the stable expression and function of CYPs and transporters in hESC-Hep and hiPSC-Hep for at least one week opens up the possibility to reproducibly perform long term and extensive studies, e.g. chronic toxicity testing, in a stem cell-derived hepatic system. (C) 2013 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2013. Vol. 86, no 5, 691-702 p.
Keyword [en]
Human embryonic stem cell-derived hepatocytes, Human induced pluripotent stem cell- derived hepatocytes, Cytochrome P450, Transporter proteins, Hepatocytes
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Natural sciences
Identifiers
URN: urn:nbn:se:his:diva-8597DOI: 10.1016/j.bcp.2013.06.029ISI: 000323404500012PubMedID: 23856292Scopus ID: 2-s2.0-84884903479OAI: oai:DiVA.org:his-8597DiVA: diva2:661014
Available from: 2013-10-31 Created: 2013-10-30 Last updated: 2016-04-20Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Holmgren, GustavKüppers-Munther, Barbara
By organisation
School of Life SciencesThe Systems Biology Research Centre
In the same journal
Biochemical Pharmacology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 290 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf