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Cardiotoxicity testing using pluripotent stem cell-derived human cardiomyocytes and state-of-the-art bioanalytics: a review
Authors:Mandenius Carl-Fredrik  Steel Daniella  Noor Fozia  Meyer Thomas  Heinzle Elmar  Asp Julia  Arain Sarina  Kraushaar Udo  Bremer Susanne  Class Reiner  Sartipy Peter
Affiliation:1. Biotechnology/IFM, Link?ping University, , Link?ping, Sweden;2. Cellartis AB, , G?teborg, Sweden;3. Biochemical Engineering, Saarland University, , Saarbruecken, Germany;4. MultiChannel Systems GmbH, , Reutlingen, Germany;5. Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, , G?teborg, Sweden;6. PerSens GmbH, , Regensburg, Germany;7. Natural and Medical Sciences Institute at the University of Tübingen, , Germany;8. ECVAM, Institute for Health and Consumer Protection (IHCP), European Commission Joint Research Center, , Ispra, Italy;9. Pharmacelsus GmbH, , Saarbruecken, Germany
Abstract:In this article, recent progress in cardiotoxicity testing based on the use of immortalized cell lines or human embryonic stem cell (hESC) derived cardiomyocytes in combination with state-of-the-art bioanalytical methods and sensors is reviewed. The focus is on hESC-derived cells and their refinement into competent testing cells, but the access and utility of other relevant cell types are also discussed. Recent developments in sensor techniques and bioanalytical approaches for measuring critical cardiotoxicity parameters are highlighted, together with aspects of data evaluation and validation. Finally, recommendations for further research are given.
Keywords:human embryonic stem cells  in vitro toxicity  cardiomyocyte  cardiotoxicity  cytotoxicity  electrophysiology  multielectrode array  surface plasmon resonance  respiration  metabolomics
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