Multi-parametric assessment of cardiomyocyte excitation-contraction coupling using impedance and field potential recording: A tool for cardiac safety assessment

Zhang, Xiaoyu; Guo, Liang; Zeng, Haoyu; White, Stephen; Furniss, Michael J.; Balasubramanian, Bharathi; Lis, Edward; Lagrutta, Armando; Sannajust, Frederick; Zhao, Li Leyna; Xi, Biao; Wang, Xiaobo; Davis, Myrtle A.; Abassi, Yama

doi:10.1016/j.vascn.2016.06.004

Cited by 62 publications

(35 citation statements)

References 38 publications

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“…The scoring system can be applied not only to various calcium-imaging-based assays but also to different detection technologies and experimental models. Using the same principal (i.e., design of the scoring matrix and the hazard labeling), the scoring system could be developed for technologies based on multi-electrode arrays (Yamazaki et al., 2018), voltage-sensitive dyes (Blinova et al., 2017, Lu et al., 2017), impedance (Zhang et al., 2016), and video motion imaging (Kopljar et al., 2017) to comprehensively account (indirectly) for APD-like parameters as well as other pharmacological responses such as BR, beat stop, and EAD-like events. Similarly, different cardiomyocyte models (primary or stem cell-derived) can be used.…”

Section: Discussionmentioning

confidence: 99%

Development of a Human iPSC Cardiomyocyte-Based Scoring System for Cardiac Hazard Identification in Early Drug Safety De-risking

et al. 2018

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SummaryHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising cardiac safety platform, demonstrated by numerous validation studies using drugs with known cardiac adverse effects in humans. However, the challenge remains to implement hiPSC-CMs into cardiac de-risking of new chemical entities (NCEs) during preclinical drug development. Here, we used the calcium transient screening assay in hiPSC-CMs to develop a hazard score system for cardiac electrical liabilities. Tolerance interval calculations and evaluation of different classes of cardio-active drugs enabled us to develop a weighted scoring matrix. This approach allowed the translation of various pharmacological effects in hiPSC-CMs into a single hazard label (no, low, high, or very high hazard). Evaluation of 587 internal NCEs and good translation to ex vivo and in vivo models for a subset of these NCEs highlight the value of the cardiac hazard scoring in facilitating the selection of compounds during early drug safety screening.

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Section: Discussionmentioning

confidence: 99%

Development of a Human iPSC Cardiomyocyte-Based Scoring System for Cardiac Hazard Identification in Early Drug Safety De-risking

et al. 2018

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“…Yang and Papoian [ 140 ] have recently suggested to complement the electrophysiological evaluation of the CiPA platform by adding a structural assessment of hiPSCs-CMs, thus, allowing to analyze both potential proarrhythmic and non-proarrhythmic effects on cardiac contractility. Even if the in vitro screening assays for cardiotoxicity are predominately focused on identifying proarrhythmia risk, some platforms have already been developed to detect both proarrhythmic and structural toxicities [ 141 ]. Importantly, this combined approach provide an integrated structural and electrophysiological assessment in CMs that might better predict the drug-induced contractility changes.…”

Section: The Promise Of Hipscs-cms In Biomedical Applicationsmentioning

confidence: 99%

Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications

Baldassarre

Cimetta

Bollini

et al. 2018

Cells

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Human-induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as sources of cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs; the methods used to improve scalability of throughput assays for functional screening and drug testing in vitro; the phenotypic characteristics of hiPSCs-derived CMs and their ability to rescue injured CMs through paracrine effects; we also cover the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their immunological features and the potential use in biomedical applications.

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“…Both of them have been considered physiologically relevant functional outputs to be used in pre-clinical safety evaluation [ 101 ]. Multielectrode arrays technology (MEA), which measures extracellular voltage and/or electrical impedance to obtain information about CM contractibility and electrophysiology properties, is a commonly used platform [ 130 ]. However, these devices are generally not compatible with 3D cardiac tissues, since cells need to be in direct contact with the electrodes.…”

Section: In Vitro Applications Of Hpsc-derived 3d Cardiac Microtismentioning

confidence: 99%

From Human Pluripotent Stem Cells to 3D Cardiac Microtissues: Progress, Applications and Challenges

Branco

Diogo

2020

Bioengineering

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The knowledge acquired throughout the years concerning the in vivo regulation of cardiac development has promoted the establishment of directed differentiation protocols to obtain cardiomyocytes (CMs) and other cardiac cells from human pluripotent stem cells (hPSCs), which play a crucial role in the function and homeostasis of the heart. Among other developments in the field, the transition from homogeneous cultures of CMs to more complex multicellular cardiac microtissues (MTs) has increased the potential of these models for studying cardiac disorders in vitro and for clinically relevant applications such as drug screening and cardiotoxicity tests. This review addresses the state of the art of the generation of different cardiac cells from hPSCs and the impact of transitioning CM differentiation from 2D culture to a 3D environment. Additionally, current methods that may be employed to generate 3D cardiac MTs are reviewed and, finally, the adoption of these models for in vitro applications and their adaptation to medium- to high-throughput screening settings are also highlighted.

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Multi-parametric assessment of cardiomyocyte excitation-contraction coupling using impedance and field potential recording: A tool for cardiac safety assessment

Cited by 62 publications

References 38 publications

Development of a Human iPSC Cardiomyocyte-Based Scoring System for Cardiac Hazard Identification in Early Drug Safety De-risking

Development of a Human iPSC Cardiomyocyte-Based Scoring System for Cardiac Hazard Identification in Early Drug Safety De-risking

Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications

From Human Pluripotent Stem Cells to 3D Cardiac Microtissues: Progress, Applications and Challenges

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