An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes
The ability to produce unlimited numbers of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) harboring disease and patient-specific gene variants creates a new paradigm for modeling congenital heart diseases (CHDs) and predicting proarrhythmic liabilities of drug candidates. Ho...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-10-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2017.00766/full |
| _version_ | 1828769352131805184 |
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| author | Wesley L. McKeithan Wesley L. McKeithan Alex Savchenko Michael S. Yu Michael S. Yu Fabio Cerignoli Arne A. N. Bruyneel Jeffery H. Price Alexandre R. Colas Evan W. Miller John R. Cashman Mark Mercola |
| author_facet | Wesley L. McKeithan Wesley L. McKeithan Alex Savchenko Michael S. Yu Michael S. Yu Fabio Cerignoli Arne A. N. Bruyneel Jeffery H. Price Alexandre R. Colas Evan W. Miller John R. Cashman Mark Mercola |
| author_sort | Wesley L. McKeithan |
| collection | DOAJ |
| description | The ability to produce unlimited numbers of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) harboring disease and patient-specific gene variants creates a new paradigm for modeling congenital heart diseases (CHDs) and predicting proarrhythmic liabilities of drug candidates. However, a major roadblock to implementing hiPSC-CM technology in drug discovery is that conventional methods for monitoring action potential (AP) kinetics and arrhythmia phenotypes in vitro have been too costly or technically challenging to execute in high throughput. Herein, we describe the first large-scale, fully automated and statistically robust analysis of AP kinetics and drug-induced proarrhythmia in hiPSC-CMs. The platform combines the optical recording of a small molecule fluorescent voltage sensing probe (VoltageFluor2.1.Cl), an automated high throughput microscope and automated image analysis to rapidly generate physiological measurements of cardiomyocytes (CMs). The technique can be readily adapted on any high content imager to study hiPSC-CM physiology and predict the proarrhythmic effects of drug candidates. |
| first_indexed | 2024-12-11T13:46:18Z |
| format | Article |
| id | doaj.art-dd6ff2dfd36f4a7aa83cff65a91e103a |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-11T13:46:18Z |
| publishDate | 2017-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-dd6ff2dfd36f4a7aa83cff65a91e103a2022-12-22T01:04:29ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2017-10-01810.3389/fphys.2017.00766277220An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived CardiomyocytesWesley L. McKeithan0Wesley L. McKeithan1Alex Savchenko2Michael S. Yu3Michael S. Yu4Fabio Cerignoli5Arne A. N. Bruyneel6Jeffery H. Price7Alexandre R. Colas8Evan W. Miller9John R. Cashman10Mark Mercola11Department of Medicine, Cardiovascular Institute, Stanford University, Stanford, CA, United StatesGraduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United StatesDepartment of Medicine, Cardiovascular Institute, Stanford University, Stanford, CA, United StatesSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United StatesDepartment of Bioengineering, University of California, San Diego, San Diego, CA, United StatesVala Sciences, San Diego, CA, United StatesDepartment of Medicine, Cardiovascular Institute, Stanford University, Stanford, CA, United StatesVala Sciences, San Diego, CA, United StatesSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United StatesDepartments of Chemistry, Molecular and Cell Biology, Helen Wills Neuroscience, University of California, Berkeley, Berkeley, CA, United StatesHuman BioMolecular Research Institute, San Diego, CA, United StatesDepartment of Medicine, Cardiovascular Institute, Stanford University, Stanford, CA, United StatesThe ability to produce unlimited numbers of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) harboring disease and patient-specific gene variants creates a new paradigm for modeling congenital heart diseases (CHDs) and predicting proarrhythmic liabilities of drug candidates. However, a major roadblock to implementing hiPSC-CM technology in drug discovery is that conventional methods for monitoring action potential (AP) kinetics and arrhythmia phenotypes in vitro have been too costly or technically challenging to execute in high throughput. Herein, we describe the first large-scale, fully automated and statistically robust analysis of AP kinetics and drug-induced proarrhythmia in hiPSC-CMs. The platform combines the optical recording of a small molecule fluorescent voltage sensing probe (VoltageFluor2.1.Cl), an automated high throughput microscope and automated image analysis to rapidly generate physiological measurements of cardiomyocytes (CMs). The technique can be readily adapted on any high content imager to study hiPSC-CM physiology and predict the proarrhythmic effects of drug candidates.http://journal.frontiersin.org/article/10.3389/fphys.2017.00766/fullinduced pluripotent stem cellscardiomyocytevoltage sensitive probehigh throughput screeningdrug developmentcardiotoxicity |
| spellingShingle | Wesley L. McKeithan Wesley L. McKeithan Alex Savchenko Michael S. Yu Michael S. Yu Fabio Cerignoli Arne A. N. Bruyneel Jeffery H. Price Alexandre R. Colas Evan W. Miller John R. Cashman Mark Mercola An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes Frontiers in Physiology induced pluripotent stem cells cardiomyocyte voltage sensitive probe high throughput screening drug development cardiotoxicity |
| title | An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes |
| title_full | An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes |
| title_fullStr | An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes |
| title_full_unstemmed | An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes |
| title_short | An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes |
| title_sort | automated platform for assessment of congenital and drug induced arrhythmia with hipsc derived cardiomyocytes |
| topic | induced pluripotent stem cells cardiomyocyte voltage sensitive probe high throughput screening drug development cardiotoxicity |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2017.00766/full |
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