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One Standardized Differentiation Procedure Robustly Generates Homogenous Hepatocyte Cultures Displaying Metabolic Diversity from a Large Panel of Human Pluripotent Stem Cells
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden. (Bioinformatik, Bioinformatics)ORCID iD: 0000-0003-1174-3611
Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden / Novo Nordisk A/S, Bagsværd, Denmark.
Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden.
Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden.
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2016 (English)In: Stem Cell Reviews, ISSN 1550-8943, E-ISSN 1558-6804, Vol. 12, no 1, 90-104 p.Article in journal (Refereed) Published
Abstract [en]

Human hepatocytes display substantial functional inter-individual variation regarding drug metabolizing functions. In order to investigate if this diversity is mirrored in hepatocytes derived from different human pluripotent stem cell (hPSC) lines, we evaluated 25 hPSC lines originating from 24 different donors for hepatic differentiation and functionality. Homogenous hepatocyte cultures could be derived from all hPSC lines using onestandardized differentiation procedure. To the best of our knowledge this is the first report of a standardized hepatic differentiation procedure that is generally applicable across a large panel of hPSC lines without any adaptations to individual lines. Importantly, with regard to functional aspects, such as Cytochrome P450 activities, we observed that hepatocytes derived from different hPSC lines displayed inter-individual variation characteristic for primary hepatocytes obtained from different donors, while these activities were highly reproducible between repeated experiments using the same line. Taken together, these data demonstrate the emerging possibility to compile panels of hPSC-derived hepatocytes of particular phenotypes/genotypes relevant for drug metabolism and toxicity studies. Moreover, these findings are of significance for applications within the regenerative medicine field, since our stringent differentiation procedure allows the derivation of homogenous hepatocyte cultures from multiple donors which is a prerequisite for the realization of future personalized stem cell based therapies.

Place, publisher, year, edition, pages
Springer, 2016. Vol. 12, no 1, 90-104 p.
Keyword [en]
Cellular therapy, Hepatocyte differentiation, Human embyronic stem cells, Human induced pluripotent stem cells, Liver, Toxicity
National Category
Cell and Molecular Biology
Research subject
Medical sciences
Identifiers
URN: urn:nbn:se:his:diva-11781DOI: 10.1007/s12015-015-9621-9ISI: 000374582000008PubMedID: 26385115Scopus ID: 2-s2.0-84955335024OAI: oai:DiVA.org:his-11781DiVA: diva2:890175
Available from: 2015-12-31 Created: 2015-12-31 Last updated: 2016-06-09Bibliographically approved

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