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High Content Analysis of Human Pluripotent Stem Cell Derived Hepatocytes Reveals Drug Induced Steatosis and Phospholipidosis
Takara Bio Europe AB (Former Cellectis AB/Cellartis AB), Göteborg, Sweden / Novo Nordisk A/S, Stem Cell Development, Bagsværd, Denmark.
Takara Bio Europe AB (Former Cellectis AB/Cellartis AB), Göteborg, Sweden / Horizon Discovery Ltd, Cambridge Research Park, Cambridge, UK.
Takara Bio Europe AB (Former Cellectis AB/Cellartis AB), Göteborg, Sweden.
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Takara Bio Europe AB (Former Cellectis AB/Cellartis AB), Göteborg, Sweden. (Bioinformatik, Bioinformatics)ORCID iD: 0000-0002-0402-1437
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2016 (English)In: Stem Cells International, ISSN 1687-9678, Vol. 2016, 2475631Article in journal (Refereed) Published
Abstract [en]

Hepatotoxicity is one of the most cited reasons for withdrawal of approved drugs from the market. The use of nonclinically relevant in vitro and in vivo testing systems contributes to the high attrition rates. Recent advances in differentiating human induced pluripotent stem cells (hiPSCs) into pure cultures of hepatocyte-like cells expressing functional drug metabolizing enzymes open up possibilities for novel, more relevant human cell based toxicity models. The present study aimed to investigate the use of hiPSC derived hepatocytes for conducting mechanistic toxicity testing by image based high content analysis (HCA). The hiPSC derived hepatocytes were exposed to drugs known to cause hepatotoxicity through steatosis and phospholipidosis, measuring several endpoints representing different mechanisms involved in drug induced hepatotoxicity. The hiPSC derived hepatocytes were benchmarked to the HepG2 cell line and generated robust HCA data with low imprecision between plates and batches. The different parameters measured were detected at subcytotoxic concentrations and the order of which the compounds were categorized (as severe, moderate, mild, or nontoxic) based on the degree of injury at isomolar concentration corresponded to previously published data. Taken together, the present study shows how hiPSC derived hepatocytes can be used as a platform for screening drug induced hepatotoxicity by HCA.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2016. Vol. 2016, 2475631
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:his:diva-12039DOI: 10.1155/2016/2475631ISI: 000371516600001PubMedID: 26880940ScopusID: 2-s2.0-84955472147OAI: oai:DiVA.org:his-12039DiVA: diva2:912065
Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2017-03-07Bibliographically approved

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