One Standardized Differentiation Procedure Robustly Generates Homogenous Hepatocyte Cultures Displaying Metabolic Diversity from a Large Panel of Human Pluripotent Stem Cells.
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 one standardized 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.
['Asplund|Annika|A|', 'Pradip|Arvind|A|', 'van Giezen|Mariska|M|', 'Aspegren|Anders|A|', 'Choukair|Helena|H|', 'Rehnström|Marie|M|', 'Jacobsson|Susanna|S|', 'Ghosheh|Nidal|N|', 'El Hajjam|Dorra|D|', 'Holmgren|Sandra|S|', 'Larsson|Susanna|S|', 'Benecke|Jörg|J|', 'Butron|Mariela|M|', 'Wigander|Annelie|A|', 'Noaksson|Karin|K|', 'Sartipy|Peter|P|', 'Björquist|Petter|P|', 'Edsbagge|Josefina|J|', 'Küppers-Munther|Barbara|B|http://orcid.org/0000-0003-4217-9355']
D018929:Cell Culture Techniques D002454:Cell Differentiation D002460:Cell Line D003470:Culture Media D003577:Cytochrome P-450 Enzyme System D015870:Gene Expression D022781:Hepatocytes D006801:Humans D008658:Inactivation, Metabolic D007527:Isoenzymes D007621:Karyotyping D009928:Organ Specificity D039904:Pluripotent Stem Cells D061251:Primary Cell Culture D015203:Reproducibility of Results
Toxicity Cellular therapy Hepatocyte differentiation Human embyronic stem cells Human induced pluripotent stem cells Liver