Assessment of extracellular field potential and Ca2+ transient signals for early QT/pro-arrhythmia detection using human induced pluripotent stem cell-derived cardiomyocytes

Abi‐Gerges, Najah; Pointon, Amy; Oldman, Karen; Brown, M.; Pilling, Mark; Sefton, C.; Garside, Helen; Pollard, Chris

doi:10.1016/j.vascn.2016.09.001

Cited by 32 publications

(23 citation statements)

References 68 publications

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“…Maximum recorded voltages increased in a similar trend, independent of culture substrate (nylon or control well surface). The key advantage of recording electrophysiological data from the nylon mesh is that functional circuits may be selectively cultured as there is a growing interest in 3D functional physiology . Recordings can be compared between nylon meshes in various studies relevant to peripheral nerve regeneration in this instance through paracrine signaling or pharmacological treatment manipulations .…”

Section: Discussionmentioning

confidence: 99%

“…The key advantage of recording electrophysiological data from the nylon mesh is that functional circuits may be selectively cultured as there is a growing interest in 3D functional physiology. 49 Recordings can be compared between nylon meshes in various studies relevant to peripheral nerve regeneration in this instance through paracrine signaling or pharmacological treatment manipulations. 50 Whilst still permitting 3D cell-to-cell interactions, the current nylon mesh can allow for neuronal electrophysiology to be manipulated and analyzed.…”

Section: Electrophysiological Recording Of Ng108-15 Cells On Nylonmentioning

confidence: 99%

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Nylon as an in vitro scaffold for three‐dimensional study of neural cells

Batth

Thompson

2018

J Biomedical Materials Res

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The requirement for improved modeling of cells in culture for study of cell-to-cell interactions has led to an increased focus on three-dimensional (3D) in vitro models. In this study, NG108-15 neural cells and rat sciatic nerve Schwann cells were successfully grown as monocultures and as a coculture on the biocompatible nylon mesh substrates. This has allowed proliferation and interactions between the two cell types to be monitored on the mesh over time. Electrophysiological recordings validated the NG108-15 neural cell differentiation which confirmed the similarity of recorded action potentials in two-dimensional culture environments. A variety of assays have been used, demonstrating the use of nylon as an appropriate substrate for neural cell in vitro studies, and nylon can easily be imaged using inverted microscopy. These studies confirm the suitability of the nylon 3D culture presented for modeling neural cell behavior. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1575-1584, 2018.

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Section: Discussionmentioning

confidence: 99%

Section: Electrophysiological Recording Of Ng108-15 Cells On Nylonmentioning

confidence: 99%

Nylon as an in vitro scaffold for three‐dimensional study of neural cells

Batth

Thompson

2018

J Biomedical Materials Res

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“…19,20 To address this limitation, various two-dimensional (2-D) and 3-D human cardiac models have been developed. Monolayer assays have focused heavily on electrophysiology for detecting arrhythmogenicity, but the predictability is variable 13,[21][22][23] unless the structural and functional anisotropic properties of the native ventricle are reproduced by enforcing biomimetic cell alignment. [23][24][25][26][27] While aligned monolayers are useful for studying electrophysiology, they are not amenable to contractility measurements.…”

Section: What Does This Study Add To Our Knowledge?mentioning

confidence: 99%

“…Human pluripotent stem cell (hPSC)‐derived ventricular cardiomyocytes (CMs) as bona fide human heart cells have been proposed to fill this gap . Earlier single‐cell experiments focused on viability and cellular responses such as electrophysiology as gauged by patch‐clamp and Ca 2+ recordings for cardiotoxicity screening . While these simpler models offer improvements as a first level of screening, they cannot capture physiologically complex multi cellular or tissue‐level phenomena.…”

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confidence: 99%

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Human Cardiac Ventricular‐Like Organoid Chambers and Tissue Strips From Pluripotent Stem Cells as a Two‐Tiered Assay for Inotropic Responses

Keung

Chan

Backeris

et al. 2019

Clin Pharma and Therapeutics

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Traditional drug discovery is an inefficient process. Human pluripotent stem cell‐derived cardiomyocytes can potentially fill the gap between animal and clinical studies, but conventional two‐dimensional cultures inadequately recapitulate the human cardiac phenotype. Here, we systematically examined the pharmacological responses of engineered human ventricular‐like cardiac tissue strips (hvCTS) and organoid chambers (hvCOC) to 25 cardioactive compounds covering various drug classes. While hvCTS effectively detected negative and null inotropic effects, the sensitivity to positive inotropes was modest. We further quantified the predictive capacity of hvCTS in a blinded screening, with accuracies for negative, positive, and null inotropic effects at 100%, 86%, and 80%, respectively. Interestingly, hvCOC, with a pro‐maturation milieu that yields physiologically complex parameters, displayed enhanced positive inotropy. Based on these results, we propose a two‐tiered screening system for avoiding false positives and negatives. Such an approach would facilitate drug discovery by leading to better overall success.

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