Abstract
Microelectrode arrays (MEAs) are widely used to assess the electrophysiology of human pluripotent stem cell-derived cardiomyocytes (hPS-CMs). Traditionally, MEAs have been used to record data at the cell population level, but it would be beneficial to be able to analyze also at the single-cell level using MEAs. To realize this, we present a special MEA platform for recording field potential from single beating cardiomyocytes. The size and location of transparent indium tin oxide (ITO) electrodes have been optimized to make noninvasive studies of the electrophysiological activity of cardiomyocytes at the single-cell level possible and also to enable simultaneous video imaging through transparent electrodes and thus image-based analysis of the mechanical beating behavior of the same cardiomyocytes. Because of these characteristics, this novel platform provides a powerful tool for assessing the functionality of cardiomyocytes in basic cardiac research, disease modeling, as well as drug development and toxicology.
Highlights
Microelectrode arrays (MEAs) provide a valuable tool for studying the electrophysiology of cells
They are suitable for modeling human cardiomyocytes and use in studies of human heart development, cardiac function, and diseases as well as in drug development and toxicology, as reviewed earlier.8) human pluripotent stem cell-derived cardiomyocytes (hPS-CMs) have been used in the evaluation of cardiac safety of new drug candidates especially for their effects on the field potential duration (FPD), which is analogous to the QT interval of electrocardiography (ECG).9)
3.1 MEA layout development and technical characterization In Layout 1, the cells plated on the MEA attached to the electrodes with high probability as the finger-type electrodes filled most of the cell culture area
Summary
Microelectrode arrays (MEAs) provide a valuable tool for studying the electrophysiology of cells. Human induced pluripotent stem (iPS) cells are derived from somatic cells with a defined set of factors.5) They can be differentiated, e.g., into cardiomyocytes (CMs) by multiple methods, such as using defined growth factors or small molecules, or by co-culturing with mouse endodermal-like (END-2) cells.6,7) With the differentiation methods, all cardiac subtypes (pacemaker, atrial, and ventricular cells) can be produced and the differentiated hPS-CMs resemble the native human counterparts in their gene and protein expression as well as functional properties They are suitable for modeling human cardiomyocytes and use in studies of human heart development, cardiac function, and diseases as well as in drug development and toxicology, as reviewed earlier.8) hPS-CMs have been used in the evaluation of cardiac safety of new drug candidates especially for their effects on the field potential duration (FPD), which is analogous to the QT interval of electrocardiography (ECG).). All these aforementioned methods are either invasive or toxic to the cells and long-term experiments are not applicable
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