Predicting cardiac safety using human induced pluripotent stem cell-derived cardiomyocytes combined with multi-electrode array (MEA) technology: A conference report

Mulder, Petra; Korte, Tessa de; Dragicevic, Elena; Kraushaar, Udo; Printemps, Richard; Vlaming, Maria L. H.; Braam, Stefan; Valentin, Jean‐Pierre

doi:10.1016/j.vascn.2018.01.003

Cited by 23 publications

(4 citation statements)

References 46 publications

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“…Table 2 shows the changes observed in human iPSC‐cardiomyocytes in all recorded parameters in response to CLQ, OH‐CLQ, AZI, and ERT, alone or in combination. Minimum concentrations that produced more than 20% change (considered as threshold for biological relevance in this model) 37 as compared with DMSO are reported. CLQ and OH‐CLQ caused concentration‐dependent beat rate decrease.…”

Section: Resultsmentioning

confidence: 99%

Applying the CiPA approach to evaluate cardiac proarrhythmia risk of some antimalarials used off‐label in the first wave of COVID‐19

Delaunois

Abernathy

Anderson

et al. 2021

Clinical Translational Sci

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We applied a set of in silico and in vitro assays, compliant with the CiPA (Comprehensive In Vitro Proarrhythmia Assay) paradigm, to assess the risk of chloroquine or hydroxychloroquine‐mediated QT prolongation and Torsades de Pointes (TdP), alone and combined with erythromycin and azithromycin, drugs repurposed during the first wave of COVID‐19. Each drug or drug combination was tested in patch clamp assays on 7 cardiac ion channels, in in silico models of human ventricular electrophysiology (Virtual Assay ® ) using control (healthy) or high‐risk cell populations, and in human induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes. In each assay, concentration‐response curves encompassing and exceeding therapeutic free plasma levels were generated. Both chloroquine and hydroxychloroquine showed blocking activity against some potassium, sodium and calcium currents. Chloroquine and hydroxychloroquine inhibited I Kr (IC 50 : 1µM and 3‐7µM, respectively) and I K1 currents (IC 50 : 5 and 44µM, respectively). When combining hydroxychloroquine with azithromycin, no synergistic effects were observed. The two macrolides had no or very weak effects on the ion currents (IC 50 >300‐1000µM). Using Virtual Assay ® , both antimalarials affected several TdP indicators, chloroquine being more potent than hydroxychloroquine. Effects were more pronounced in the high‐risk cell population. In hiPSC‐derived cardiomyocytes, all drugs showed early‐after‐depolarizations, except azithromycin. Combining chloroquine or hydroxychloroquine with a macrolide did not aggravate their effects. In conclusion, our integrated nonclinical CiPA dataset confirmed that, at therapeutic plasma concentrations relevant for malaria or off‐label use in COVID‐19, chloroquine and hydroxychloroquine use is associated with a proarrhythmia risk, which is higher in populations carrying predisposing factors but not worsened with macrolide combination.

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Section: Resultsmentioning

confidence: 99%

Applying the CiPA approach to evaluate cardiac proarrhythmia risk of some antimalarials used off‐label in the first wave of COVID‐19

Delaunois

Abernathy

Anderson

et al. 2021

Clinical Translational Sci

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“…However, a refined method was formally demonstrated by Hubel in 1957 using electrodes with much finer tips (1–10 μm diameter) which could record neural activity from relatively smaller nerves and axons (Hubel, 1957 ). Figure 1A shows in-vitro methods which are in practice especially in pharmacological studies (Jenkinson et al, 2017 ; Mulder et al, 2018 ), investigation of neurotropic viral activity in mammalian and mosquito brain (Gaburro et al, 2018a , b ) or development of cures to neurological dysfunctions by studying the behavior of collective network activity (Md Ahsan Ul Bari and A., 2017 ; Gamble et al, 2018 ). Similarly, Figure 1B shows in-vivo methods which are prevalent in developing remedies for many neurological dysfunctions, including treatment of paralysis through stimulation (Assad et al, 2014 ; Liu et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Compatibility Evaluation of Clustering Algorithms for Contemporary Extracellular Neural Spike Sorting

Veerabhadrappa

Hassan

Zhang

et al. 2020

Front. Syst. Neurosci.

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Deciphering useful information from electrophysiological data recorded from the brain, in-vivo or in-vitro, is dependent on the capability to analyse spike patterns efficiently and accurately. The spike analysis mechanisms are heavily reliant on the clustering algorithms that enable separation of spike trends based on their spatio-temporal behaviors. Literature review report several clustering algorithms over decades focused on different applications. Although spike analysis algorithms employ only a small subset of clustering algorithms, however, not much work has been reported on the compliance and suitability of such clustering algorithms for spike analysis. In our study, we have attempted to comment on the suitability of available clustering algorithms and performance capacity when exposed to spike analysis. In this regard, the study reports a compatibility evaluation on algorithms previously employed in spike sorting as well as the algorithms yet to be investigated for application in sorting neural spikes. The performance of the algorithms is compared in terms of their accuracy, confusion matrix and accepted validation indices. Three data sets comprising of easy, difficult, and real spike similarity with known ground-truth are chosen for assessment, ensuring a uniform testbed. The procedure also employs two feature-sets, principal component analysis and wavelets. The report also presents a statistical score scheme to evaluate the performance individually and overall. The open nature of the data sets, the clustering algorithms and the evaluation criteria make the proposed evaluation framework widely accessible to the research community. We believe that the study presents a reference guide for emerging neuroscientists to select the most suitable algorithms for their spike analysis requirements.

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“…A significant case is represented by cardiotoxicity studies that evaluate drug candidates for potential cardiovascular liabilities, which remain today a critical factor for drug discovery and development due to the high incidence of heart-related adverse drug effects (Edwards and Aronson, 2000;Li et al, 2017;Mulder et al, 2018). In fact, the pharmaceutical industry still relies on the Automated Patch-Clamp (APC) method to assess cardiac safety, although this technique is showing low power of predictivity of cardiac drug effects due to intrinsic limitations.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Recording of Human Cardiac Action Potentials on Market-Available Multielectrode Array Platforms

Melle

Bruno

Maccaferri

et al. 2020

Front. Bioeng. Biotechnol.

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High quality attenuated intracellular action potentials from large cell networks can be recorded on multi-electrode arrays by means of 3D vertical nanopillars using electrical pulses. However, most of the techniques require complex 3D nanostructures that prevent the straightforward translation into marketable products and the wide adoption in the scientific community. Moreover, 3D nanostructures are often delicate objects that cannot sustain several harsh use/cleaning cycles. On the contrary, laser optoacoustic poration allows the recording of action potentials on planar nanoporous electrodes made of noble metals. However, these constraints of the electrode material and morphology may also hinder the full exploitation of this methodology. Here, we show that optoacoustic poration is also very effective for porating cells on a large family of MEA electrode configurations, including robust electrodes made of nanoporous titanium nitride or disordered fractal-like gold nanostructures. This enables the recording of high quality cardiac action potentials in combination with optoacoustic poration, providing thus attenuated intracellular recordings on various already commercial devices used by a significant part of the research and industrial communities.

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Predicting cardiac safety using human induced pluripotent stem cell-derived cardiomyocytes combined with multi-electrode array (MEA) technology: A conference report

Cited by 23 publications

References 46 publications

Applying the CiPA approach to evaluate cardiac proarrhythmia risk of some antimalarials used off‐label in the first wave of COVID‐19

Applying the CiPA approach to evaluate cardiac proarrhythmia risk of some antimalarials used off‐label in the first wave of COVID‐19

Compatibility Evaluation of Clustering Algorithms for Contemporary Extracellular Neural Spike Sorting

Intracellular Recording of Human Cardiac Action Potentials on Market-Available Multielectrode Array Platforms

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