ArticleJournal of biomolecular screening2015
A new system for profiling drug-induced calcium signal perturbation in human embryonic stem cell-derived cardiomyocytes.
Article in Journal of biomolecular screening, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Systems for the Functional Evaluation of Human Heart Tissues Derived from Pluripotent Stem Cells.Stem cells (Dayton, Ohio) · 2022Review
- GPCR mediated control of calcium dynamics: A systems perspective.Cellular signalling · 2020Review
- Modification of distinct ion channels differentially modulates CaScientific reports · 2017Article
- Comprehensive Translational Assessment of Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes for Evaluating Drug-Induced Arrhythmias.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform.Biochimica et biophysica acta · 2016Article
- A Systemized Approach to Investigate Ca(2+) Synchronization in Clusters of Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes.Frontiers in cell and developmental biology · 2015Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The emergence of human stem cell-derived cardiomyocyte (hSCCM)-based assays in the cardiovascular (CV) drug discovery sphere requires the development of improved systems for interrogating the rich information that these cell models have the potential to yield. We developed a new analytical framework termed SALVO (synchronization, amplitude, length, and variability of oscillation) to profile the amplitude and temporal patterning of intra- and intercellular calcium signals in hSCCM. SALVO quantified drug-induced perturbations in the calcium signaling "fingerprint" in spontaneously contractile hSCCM. Multiparametric SALVO outputs were integrated into a single index of in vitro cytotoxicity that confirmed the rank order of perturbation as astemizole > thioridazine > cisapride > flecainide > valdecoxib > sotalol > nadolol ≈ control. This rank order of drug-induced Ca(2+) signal disruption is in close agreement with the known arrhythmogenic liabilities of these compounds in humans. Validation of the system using a second set of compounds and hierarchical cluster analysis demonstrated the utility of SALVO to discriminate drugs based on their mechanisms of action. We discuss the utility of this new mechanistically agnostic system for the evaluation of in vitro drug cytotoxicity in hSCCM syncytia and the potential placement of SALVO in the early stage drug screening framework.
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Registered trials
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