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Related Experiment Video

Updated: May 13, 2026

Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction

Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction

Published on: November 3, 2011

Stem cell-derived cardiomyocytes demonstrate arrhythmic potential.

Ying Ming Zhang¹, Criss Hartzell, Michael Narlow

¹Department of Medicine, Emory University, Atlanta, Ga 30033, USA.

|September 5, 2002

Summary

Embryonic stem cells (ESCs) and embryonal carcinoma cells (ECCs) differentiated into cardiomyocytes exhibit arrhythmogenic properties, including spontaneous activity and triggered arrhythmias, cautioning against their use in cell therapy.

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Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction

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High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers

Published on: March 24, 2023

Area of Science:

Cardiology
Stem Cell Biology
Electrophysiology

Background:

Cardiomyocytes (CMs) derived from embryonic stem cells (ESCs) and embryonal carcinoma cells (ECCs) possess some, but not all, adult myocyte characteristics.
ESCs demonstrate engraftment potential in damaged myocardium, suggesting therapeutic applications for cardiomyopathy.
The arrhythmogenic properties of ESC- and ECC-derived CMs require thorough investigation.

Purpose of the Study:

To investigate the arrhythmogenic potential of cardiomyocytes differentiated from mouse ESCs and ECCs.
To characterize the electrophysiological properties and identify potential arrhythmia mechanisms in these derived CMs.

Main Methods:

Whole-cell patch-clamp recordings were utilized to study cardiomyocytes in vitro.
Action potential (AP) morphology, upstroke velocity (dV/dt), and AP duration were analyzed.
Pharmacological agents and ionic manipulations were employed to induce and assess triggered activity and afterdepolarizations.

Main Results:

Derived CMs exhibited significant AP morphology heterogeneity, reduced maximum dV/dt, and prolonged AP durations.
Spontaneous electrical activity and frequent triggered activity were observed in cultured CMs.
Early afterdepolarizations (EADs) were inducible under various conditions, including pharmacological stimulation and ionic changes.
Delayed afterdepolarizations (DADs) were readily induced by hypercalcemia or isoproterenol.

Conclusions:

ESC- and ECC-derived CMs differentiate into at least three distinct AP phenotypes.
These CMs display spontaneous activity, impaired dV/dt, prolonged AP duration, and readily inducible triggered arrhythmias.
The findings necessitate caution regarding the use of ESCs in cell transplantation therapy due to their potential to induce arrhythmias via reentry, automaticity, or triggered activity.