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Review
. 2019 Oct 28;8(11):1331.
doi: 10.3390/cells8111331.

hiPSCs Derived Cardiac Cells for Drug and Toxicity Screening and Disease Modeling: What Micro- Electrode-Array Analyses Can Tell Us

Sophie Kussauer  1 , Robert David  2 , Heiko Lemcke  3
Affiliations
Review

hiPSCs Derived Cardiac Cells for Drug and Toxicity Screening and Disease Modeling: What Micro- Electrode-Array Analyses Can Tell Us

Sophie Kussauer et al. Cells. .

Abstract

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) have been intensively used in drug development and disease modeling. Since iPSC-cardiomyocyte (CM) was first generated, their characterization has become a major focus of research. Multi-/micro-electrode array (MEA) systems provide a non-invasive user-friendly platform for detailed electrophysiological analysis of iPSC cardiomyocytes including drug testing to identify potential targets and the assessment of proarrhythmic risk. Here, we provide a systematical overview about the physiological and technical background of micro-electrode array measurements of iPSC-CM. We introduce the similarities and differences between action- and field potential and the advantages and drawbacks of MEA technology. In addition, we present current studies focusing on proarrhythmic side effects of novel and established compounds combining MEA systems and iPSC-CM. MEA technology will help to open a new gateway for novel therapies in cardiovascular diseases while reducing animal experiments at the same time.

Keywords: MEA; cardiomyocytes; drug/toxicity screening; field potential; micro-electrode-array; multi-electrode-array.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
(A) Glass multi-/micro-electrode array (MEA) chip used to detect field potential (FP) of cells. (B) Cells seeded on an MEA surface, grown on top of the electrodes (black dots), Video S1.
Figure 2
Figure 2
(A) Subtype specific pattern of the cardiac action potential. Ventricular, atrial and nodal cells are characterized by unique depolarization and repolarization processes leading to different action potential (AP) waveforms. Numbers correspond to the different phases that reflect the activity of involved ion channels. (B) Comparison of the different phases between recorded action potential and field potential. As field potential measurements allow reconstruction of the corresponding action potential it provides important physiological parameters of electrically active cells, including spike amplitude, FP interval, etc. (C) Moreover, MEA analysis can be applied to obtain data about prolongation velocity and direction of the field potential spreading throughout the cell layer.
Figure 3
Figure 3
Increase of PubMed listed publications involving MEA based analysis of “heart” or “drugs” over the last five decades. The terms (multielectrode array and drug) or (microelectrode array and drug) and (multielectrode array and heart) or (microelectrode array and heart) were used for the PubMed search (date: Sept 2019).
See this image and copyright information in PMC

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