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Hepatic differentiation and maturation of human embryonic stem cells cultured in a perfused three-dimensional bioreactor
Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
Cellectis Stem Cells, Cellartis AB, Göteborg, Sweden.
Cellectis Stem Cells, Cellartis AB, Göteborg, Sweden.
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2013 (English)In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 22, no 4, 581-594 p.Article in journal (Refereed) Published
Abstract [en]

Drug-induced liver injury is a serious and frequently occurring adverse drug reaction in the clinics and is hard to predict during preclinical studies. Today, primary hepatocytes are the most frequently used cell model for drug discovery and prediction of toxicity. However, their use is marred by high donor variability regarding drug metabolism and toxicity, and instable expression levels of liver-specific genes such as cytochromes P450. An in vitro model system based on human embryonic stem cells (hESC), with their unique properties of pluripotency and self-renewal, has potential to provide a stable and unlimited supply of human hepatocytes. Much effort has been made to direct hESC toward the hepatic lineage, mostly using 2-dimensional (2D) cultures. Although the results are encouraging, these cells lack important functionality. Here, we investigate if hepatic differentiation of hESC can be improved by using a 3-dimensional (3D) bioreactor system. Human ESCs were differentiated toward the hepatic lineage using the same cells in either the 3D or 2D system. A global transcriptional analysis identified important differences between the 2 differentiation regimes, and we identified 10 pathways, highly related to liver functions, which were significantly upregulated in cells differentiated in the bioreactor compared to 2D control cultures. The enhanced hepatic differentiation observed in the bioreactor system was also supported by immunocytochemistry. Taken together, our results suggest that hepatic differentiation of hESC is improved when using this 3D bioreactor technology as compared to 2D culture systems. © Copyright 2013, Mary Ann Liebert, Inc. 2013.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2013. Vol. 22, no 4, 581-594 p.
Keyword [en]
article, bioreactor, cell culture, cell differentiation, cell maturation, embryonic stem cell, human, human cell, liver cell, priority journal, thre dimensional bioreactor, two dimensional culture, Bioreactors, Cell Culture Techniques, Cell Line, Drug-Induced Liver Injury, Embryonic Stem Cells, Hepatocytes, Humans, Liver, Pluripotent Stem Cells, Stem Cell Transplantation, Transplantation, Homologous
National Category
Natural Sciences
Research subject
Natural sciences
URN: urn:nbn:se:his:diva-8402DOI: 10.1089/scd.2012.0202ISI: 000314365500006PubMedID: 22970843ScopusID: 2-s2.0-84873326803OAI: diva2:640706
Available from: 2013-08-14 Created: 2013-08-14 Last updated: 2014-05-26

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Synnergren, Jane
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