OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology

Heinson, Yuli W.; Han, Julie L.; Entcheva, Emilia

doi:10.1101/2023.08.29.555447

Cited by 2 publications

References 58 publications

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Automated measurement of cardiomyocyte monolayer contraction using the Exeter Multiscope

Mohanan,

Horsell,

Watters

et al. 2024

Preprint

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We apply a novel microscope architecture, the Exeter Multiscope, to the problem of acquiring image data in rapid succession from nine wells of a 96 well plate. We demonstrate that the new microscope can detect contraction in cardiomyocyte monolayers which have been plated into these wells. Each well is sampled using 500 x 500 pixels across a 1.4 x 1.4 mm field of view, acquired in three colours at 3.7 Hz per well. The use of multiple illumination wavelengths provides post-hoc focus selection, further increasing the level of automation. The performance of the Exeter Multiscope is benchmarked against industry standard methods using a commercial microscope with a motorised stage and demonstrates that the Multiscope can acquire data almost 40 times faster. The data from both Multiscope and the commercial systems are processed by a ‘pixel variance’ algorithm that uses information from the pixel value variability over time to determine the timing and amplitude of tissue contraction. This algorithm is also benchmarked against an existing algorithm that employs an absolute difference measure of tissue contraction.

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Automated measurement of cardiomyocyte monolayer contraction using the Exeter Multiscope

Mohanan,

Horsell,

Watters

et al. 2024

Preprint

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Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for modeling cardiac arrhythmias: strengths, challenges and potential solutions

Joshi,

Albers,

Smole

et al. 2024

Front. Physiol.

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Ion channels and cytoskeletal proteins in the cardiac dyad play a critical role in maintaining excitation-contraction (E-C) coupling and provide cardiac homeostasis. Functional changes in these dyad proteins, whether induced by genetic, epigenetic, metabolic, therapeutic, or environmental factors, can disrupt normal cardiac electrophysiology, leading to abnormal E-C coupling and arrhythmias. Animal models and heterologous cell cultures provide platforms to elucidate the pathogenesis of arrhythmias for basic cardiac research; however, these traditional systems do not truly reflect human cardiac electro-pathophysiology. Notably, patients with the same genetic variants of inherited channelopathies (ICC) often exhibit incomplete penetrance and variable expressivity which underscores the need to establish patient-specific disease models to comprehend the mechanistic pathways of arrhythmias and determine personalized therapies. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) inherit the genetic background of the patient and reflect the electrophysiological characteristics of the native cardiomyocytes. Thus, iPSC-CMs provide an innovative and translational pivotal platform in cardiac disease modeling and therapeutic screening. In this review, we will examine how patient-specific iPSC-CMs historically evolved to model arrhythmia syndromes in a dish, and their utility in understanding the role of specific ion channels and their functional characteristics in causing arrhythmias. We will also examine how CRISPR/Cas9 have enabled the establishment of patient-independent and variant-induced iPSC-CMs-based arrhythmia models. Next, we will examine the limitations of using human iPSC-CMs with respect to in vitro arrhythmia modeling that stems from variations in iPSCs or toxicity due to gene editing on iPSC or iPSC-CMs and explore how such hurdles are being addressed. Importantly, we will also discuss how novel 3D iPSC-CM models can better capture in vitro characteristics and how all-optical platforms provide non-invasive and high- throughput electrophysiological data that is useful for stratification of emerging arrhythmogenic variants and drug discovery. Finally, we will examine strategies to improve iPSC-CM maturity, including powerful gene editing and optogenetic tools that can introduce/modify specific ion channels in iPSC-CMs and tailor cellular and functional characteristics. We anticipate that an elegant synergy of iPSCs, novel gene editing, 3D- culture models, and all-optical platforms will offer a high-throughput template to faithfully recapitulate in vitro arrhythmogenic events necessary for personalized arrhythmia monitoring and drug screening process.

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OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology

Cited by 2 publications

References 58 publications

Automated measurement of cardiomyocyte monolayer contraction using the Exeter Multiscope

Automated measurement of cardiomyocyte monolayer contraction using the Exeter Multiscope

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for modeling cardiac arrhythmias: strengths, challenges and potential solutions

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