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Kinetic Image Cytometry for Predicting Arrhythmias Using Human Stem Cell-Derived Cardiomyocytes

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Stem Cell-Derived Models in Toxicology

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Kinetic Image Cytometry™ (KIC™), in which living cells are cultured in multi-well dishes and imaged for electrophysiological transients (such as intracellular calcium or membrane potential) using automated digital microscopy/image analysis, represents an advance in the field of high content analysis. KIC methods, coupled with the use of human stem cell-derived cardiomyocytes (hSC-CMs), are potentially very useful for identifying proarrhythmia activity of test compounds, relevant to cardiosafety. In the present study, a panel of 40 compounds was tested with KIC to quantify the effects of the chemicals on the calcium transients associated with contraction in hSC-CMs, and the results compared to the effects of these compounds on the QT-interval from human electrocardiograms. The kinetics of the calcium transients quantified with KIC identified the chemicals that prolong (commonly associated with proarrhythmic activity) or shorten the QT interval with 100 % specificity and 94 % sensitivity. These data, along with data obtained in previous studies utilizing KIC and hSC-CMs, demonstrate that this assay platform represents the current “state-of-the-art” in vitro method for testing drug candidates for proarrhythmic tendencies.

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Acknowledgements

We would like to gratefully acknowledge Axiogenesis for contribution of the hES-CMs used in this study. Development of KIC instrumentation and methods and CyteSeer™ has been supported by several grants including the following: NIH/NHLBI FastTrack STTR R42HL086076 “Live cell and HCS assays to quantify production of cardiomyocytes from stem cells”; CIRM RT1-01143 “Optimization in the Identification, Selection and Induction of Maturation of Subtypes of Cardiomyocytes derived from Human Embryonic Stem Cells”; and NIH/NHLBI STTR R42HL112521 “Optogenetic Multiparametric Assay for HT Cardiotoxicity Testing.”

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Authors and Affiliations

  1. Vala Sciences, 6370 Nancy Ridge Dr. #106, San Diego, CA, 92121, USA

    Emily R. Pfeiffer, Ross Whittaker, Raquel Vega, Fabio Cerignoli, Patrick M. McDonough & Jeffrey H. Price

Authors
  1. Emily R. Pfeiffer
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  2. Ross Whittaker
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  3. Raquel Vega
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  4. Fabio Cerignoli
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  5. Patrick M. McDonough
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  6. Jeffrey H. Price
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Corresponding author

Correspondence to Patrick M. McDonough .

Editor information

Editors and Affiliations

  1. Axion BioSystems, Inc., Atlanta, Georgia, USA

    Mike Clements

  2. Cell Applications, GE Healthcare, Cardiff, United Kingdom

    Liz Roquemore

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Pfeiffer, E.R., Whittaker, R., Vega, R., Cerignoli, F., McDonough, P.M., Price, J.H. (2017). Kinetic Image Cytometry for Predicting Arrhythmias Using Human Stem Cell-Derived Cardiomyocytes. In: Clements, M., Roquemore, L. (eds) Stem Cell-Derived Models in Toxicology. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6661-5_8

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  • DOI: https://doi.org/10.1007/978-1-4939-6661-5_8

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6659-2

  • Online ISBN: 978-1-4939-6661-5

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