Multi-scale electrophysiological characterization of human cardioids reveals progressive maturation
Background: Human induced pluripotent stem cell-derived cardiomyocytes are valuable for cardiac disease modelling and drug testing but remain limited by immature structural and electrophysiological properties in conventional two-dimensional cultures. Three-dimensional cardiac models, including cardioids, provide a more physiological environment through multicellular organization and enable…
Human stem cell-derived cardiomyocytes, known as cardioids, offer a more accurate representation of cardiac tissue due to their multicellular organization and tissue-level functionality. Researchers conducted an extensive electrophysiological analysis of cardioids over three weeks of maturation, examining resting membrane potentials, action potential amplitude and upstroke velocity, and action potential duration.
The study revealed a clear progression in these electrophysiological properties, with resting membrane potentials becoming more negative, action potential amplitudes increasing, upstroke velocity accelerating, and action potential durations shortening. These changes corresponded with higher INa density and greater expression of SCN5A mRNA and Nav1.5 protein, indicating enhanced cardiac excitability.
Early maturation stages displayed functional IKr currents, which remained stable throughout maturation. Pharmacological interventions targeting specific ion channels further elucidated the model's maturation status, demonstrating that human cardioids can serve as a valuable tool for studying ion channel-related cardiac disorders.
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