Electrophysiological characterization of drug response in hSC-derived cardiomyocytes using voltage-sensitive optical platforms

Pfeiffer-Kaushik, Emily R.; Smith, Godfrey L.; Cai, Beibei; Dempsey, Graham T.; Hortigón-Vinagre, María P.; Zamora, Víctor; Feng, Shuyun; Ingermanson, Randall; Zhu, Renjun; Hariharan, Venkatesh; Nguyen, Cuong; Pierson, Jennifer; Gintant, Gary A.; Tung, Leslie

doi:10.1016/j.vascn.2019.106612

Cited by 31 publications

(15 citation statements)

References 82 publications

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“…After the invention of patch-clamp, [1] awarded with the Noble prize in 1991, many complementary approaches have been developed to meet this challenge. They include microelectrode arrays (MEA), [2,3] CMOS nanoelectrode array (CNEA), [4] calcium imaging, [5,6] voltage-sensing optical (VSO) platforms [7] or impedance spectroscopy, [8] and others. However, each approach presents specific advantages as well as it suffers from intrinsic limitations.…”

Section: Doi: 101002/adma202004234mentioning

confidence: 99%

Mirroring Action Potentials: Label‐Free, Accurate, and Noninvasive Electrophysiological Recordings of Human‐Derived Cardiomyocytes

et al. 2021

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The electrophysiological recording of action potentials in human cells is a long‐sought objective due to its pivotal importance in many disciplines. Among the developed techniques, invasiveness remains a common issue, causing cytotoxicity or altering unpredictably cell physiological response. In this work, a new approach for recording intracellular signals of outstanding quality and with noninvasiveness is introduced. By taking profit of the concept of mirror charge in classical electrodynamics, the new proposed device transduces cell ionic currents into mirror charges in a microfluidic chamber, thus realizing a virtual mirror cell. By monitoring mirror charge dynamics, it is possible to effectively record the action potentials fired by the cells. Since there is no need for accessing or interacting with the cells, the method is intrinsically noninvasive. In addition, being based on optical recording, it shows high spatial resolution and high parallelization. As shown through a set of experiments, the presented methodology is an ideal candidate for the next generation devices for the reliable assessment of cardiotoxicity on human‐derived cardiomyocytes. More generally, it paves the way toward a new family of in vitro biodevices that will lay a new milestone in the field of electrophysiology.

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Section: Doi: 101002/adma202004234mentioning

confidence: 99%

Mirroring Action Potentials: Label‐Free, Accurate, and Noninvasive Electrophysiological Recordings of Human‐Derived Cardiomyocytes

et al. 2021

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“…The most currently employed models for the study of cardiac AP are rodent, zebrafish, and, more recently, human cardiac myocytes derived from pluripotential stem cells (or hIPSC-CMs), which are becoming popular (Figure 1). However, direct electrophysiological recording in hIPSC-CMs requires a high degree of skill, so the alternative is to perform electrophysiological studies through voltage-sensitive dyes (Pfeiffer-Kaushik et al, 2018), despite providing relevant functional results, lacks direct measurements of voltage data.…”

Section: Action Potentialmentioning

confidence: 99%

Adult and Developing Zebrafish as Suitable Models for Cardiac Electrophysiology and Pathology in Research and Industry

et al. 2021

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The electrophysiological behavior of the zebrafish heart is very similar to that of the human heart. In fact, most of the genes that codify the channels and regulatory proteins required for human cardiac function have their orthologs in the zebrafish. The high fecundity, small size, and easy handling make the zebrafish embryos/larvae an interesting candidate to perform whole animal experiments within a plate, offering a reliable and low-cost alternative to replace rodents and larger mammals for the study of cardiac physiology and pathology. The employment of zebrafish embryos/larvae has widened from basic science to industry, being of particular interest for pharmacology studies, since the zebrafish embryo/larva is able to recapitulate a complete and integrated view of cardiac physiology, missed in cell culture. As in the human heart, IKr is the dominant repolarizing current and it is functional as early as 48 h post fertilization. Finally, genome editing techniques such as CRISPR/Cas9 facilitate the humanization of zebrafish embryos/larvae. These techniques allow one to replace zebrafish genes by their human orthologs, making humanized zebrafish embryos/larvae the most promising in vitro model, since it allows the recreation of human-organ-like environment, which is especially necessary in cardiac studies due to the implication of dynamic factors, electrical communication, and the paracrine signals in cardiac function.

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“…Patient-specific iPSCs have been used to reproduce a myriad of cardiomyopathy phenotypes, including long QT syndrome, Brugada syndrome, and familial dilated cardiomyopathy [ 91 , 92 , 93 ]. The electrophysiological indices of different ion channel blockers have been assessed for their antiarrhythmic properties and proarrhythmic risks using an aniPSC-derived cardiomyocyte-based platform using a multi-electrode array system [ 94 , 95 , 96 ]. Precision medicine, such as gender and population-specific differences in drug responses, can also be tested with iPSC-derived cardiomyocytes [ 97 ].…”

Section: Strategies For Using Ipsc-based Models For Disease Modelling and Drug Testingmentioning

confidence: 99%

Application of Patient-Specific iPSCs for Modelling and Treatment of X-Linked Cardiomyopathies

Zhang

Chou

Tse

et al. 2021

IJMS

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Inherited cardiomyopathies are among the major causes of heart failure and associated with significant mortality and morbidity. Currently, over 70 genes have been linked to the etiology of various forms of cardiomyopathy, some of which are X-linked. Due to the lack of appropriate cell and animal models, it has been difficult to model these X-linked cardiomyopathies. With the advancement of induced pluripotent stem cell (iPSC) technology, the ability to generate iPSC lines from patients with X-linked cardiomyopathy has facilitated in vitro modelling and drug testing for the condition. Nonetheless, due to the mosaicism of the X-chromosome inactivation, disease phenotypes of X-linked cardiomyopathy in heterozygous females are also usually more heterogeneous, with a broad spectrum of presentation. Recent advancements in iPSC procedures have enabled the isolation of cells with different lyonisation to generate isogenic disease and control cell lines. In this review, we will summarise the current strategies and examples of using an iPSC-based model to study different types of X-linked cardiomyopathy. The potential application of isogenic iPSC lines derived from a female patient with heterozygous Danon disease and drug screening will be demonstrated by our preliminary data. The limitations of an iPSC-derived cardiomyocyte-based platform will also be addressed.

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Electrophysiological characterization of drug response in hSC-derived cardiomyocytes using voltage-sensitive optical platforms

Abstract: Electrophysiological characterization of drug response in hSC-derived cardiomyocytes using voltage-sensitive optical platforms

Cited by 31 publications

References 82 publications

Mirroring Action Potentials: Label‐Free, Accurate, and Noninvasive Electrophysiological Recordings of Human‐Derived Cardiomyocytes

Mirroring Action Potentials: Label‐Free, Accurate, and Noninvasive Electrophysiological Recordings of Human‐Derived Cardiomyocytes

Adult and Developing Zebrafish as Suitable Models for Cardiac Electrophysiology and Pathology in Research and Industry

Application of Patient-Specific iPSCs for Modelling and Treatment of X-Linked Cardiomyopathies

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