May 29, 2008Stem Cells and Development
In Vitro Electrophysiological Drug Testing Using Human Embryonic Stem Cell Derived Cardiomyocytes
Key result
Human embryonic stem cell-derived cardiomyocytes demonstrated dose-dependent prolongation of field potential duration and conduction slowing in response to known arrhythmogenic drugs.
Why the study?
Can human embryonic stem cell-derived cardiomyocytes serve as a valid in vitro model for electrophysiological drug screening and detecting pro-arrhythmic effects?
Population
Human embryonic stem cell-derived cardiomyocytes (hESC-CMs)
Design
Preclinical
Authors
Discussion
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Implication
No immediate change to drug safety testing; leaves open hESC-CM utility for pro-arrhythmia prediction.
Key Points
- This research aims to develop an in vitro assay using human embryonic stem cell-derived cardiomyocytes for drug testing and electrophysiological studies.
- Utilized human embryonic stem cell-derived cardiomyocytes (hESC-CMs) for electrophysiological drug screening.
- Performed current-clamp studies and microelectrode array (MEA) mapping to assess drug effects.
- Analyzed dose-dependent effects of various antiarrhythmic agents on action potential and conduction.
- E-4031 and Sotalol significantly increased action potential duration (p<0.05).
- Class I and III agents led to dose-dependent prolongation of corrected field potential duration (cFPD).
- Significant conduction slowing observed with sodium channel blockers and gap junction blockers (p<0.05).
Structured PICO
Can human embryonic stem cell-derived cardiomyocytes serve as a valid in vitro model for electrophysiological drug screening and detecting pro-arrhythmic effects?
P
Population
In vitro study utilizing human embryonic stem cell-derived cardiomyocytes (hESC-CMs) as a model for electrophysiological drug screening.
I
Intervention
Application of various pharmacological agents including IKr blockers (E-4031, sotalol), class I antiarrhythmics (quinidine, procainamide, propafenone), cisapride, and a gap junction blocker (1-heptanol)
O
Outcome
Electrophysiological changes including action potential duration, after-depolarizations, corrected field potential duration (cFPD), and conduction velocitysurrogate
Human embryonic stem cell-derived cardiomyocytes combined with microelectrode array mapping provide a viable in vitro model for screening drugs for pro-arrhythmic side effects.
Cite This Study
Caspi et al. (2008) studied Pro-arrhythmia. Arrhythmogenic and antiarrhythmic drugs (e.g., E-4031, Sotalol, Quinidine, Cisapride) was evaluated on Action potential duration, after-depolarizations, corrected field potential duration (cFPD), and conduction slowing. Human embryonic stem cell-derived cardiomyocytes demonstrated dose-dependent prolongation of field potential duration and conduction slowing in response to known arrhythmogenic drugs.