ArticleToxicological sciences : an official journal of the Society of Toxicology2020
Blinded, Multicenter Evaluation of Drug-induced Changes in Contractility Using Human-induced Pluripotent Stem Cell-derived Cardiomyocytes.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Induced pluripotent stem cells from discovery to translation.Nature medicine · 2026Review
- Models of the human heart for biomedical research: Opportunities and challenges.Physiological reports · 2026Review
- A simplified co-culture reveals altered cardiotoxic responses to doxorubicin in hPSC-derived cardiomyocytes in the presence of endothelial cells.Stem cell reports · 2026Article
- Investigating the Anticancer Effects of Sulforaphane in an In Vitro Coculture Model of Prostate Cancer Cells with Engineered Heart Tissue.ACS pharmacology & translational science · 2025Article
- Substrate stiffness-dependent metabolic reprogramming of iPSC-derived cardiomyocytes on physiological PDMS polymers.Metabolic engineering communications · 2025Article
- Maturation of human cardiac organoids enables complex disease modeling and drug discovery.Nature cardiovascular research · 2025Article
- Establishing a context of use for three-dimensional cardiac tissue derived from human-induced pluripotent stem cell-derived cardiomyocytes using inotropes.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Induction of cardiac alternans in human iPS-derived cardiomyocytes through β-adrenergic receptor stimulation.Physiological reports · 2024Article
- Hypertrophic cardiomyopathy dysfunction mimicked in human engineered heart tissue and improved by sodium-glucose cotransporter 2 inhibitors.Cardiovascular research · 2024Article
- Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment.iScience · 2024Article
- The new era of cardiovascular research: revolutionizing cardiovascular research with 3D models in a dish.Medical review (2021) · 2024Review
- Stem cell-derived cardiomyocytes expressing a dominant negative pacemaker HCN4 channel do not reduce the risk of graft-related arrhythmias.Frontiers in cardiovascular medicine · 2024Article
- Multifocal optical projection microscopy enables label-free 3D measurement of cardiomyocyte cluster contractility.Scientific reports · 2023Article
- Sarcomeric network analysis of ex vivo cultivated human atrial appendage tissue using super-resolution microscopy.Scientific reports · 2023Article
- High-throughput longitudinal electrophysiology screening of mature chamber-specific hiPSC-CMs using optical mapping.iScience · 2023Article
- Does Enhanced Structural Maturity of hiPSC-Cardiomyocytes Better for the Detection of Drug-Induced Cardiotoxicity?Biomolecules · 2023Article
- Research and Therapeutic Approaches in Stem Cell Genome Editing by CRISPR Toolkit.Molecules (Basel, Switzerland) · 2023Review
- Biotechnological advances and applications of human pluripotent stem cell-derived heart models.Frontiers in bioengineering and biotechnology · 2023Review
- Reproducibility of drug-induced effects on the contractility of an engineered heart tissue derived from human pluripotent stem cells.Frontiers in pharmacology · 2023Article
- Reproducibility and reporting negative data.Journal of molecular and cellular cardiology plus · 2022Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
Abstract
Animal models are 78% accurate in determining whether drugs will alter contractility of the human heart. To evaluate the suitability of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for predictive safety pharmacology, we quantified changes in contractility, voltage, and/or Ca2+ handling in 2D monolayers or 3D engineered heart tissues (EHTs). Protocols were unified via a drug training set, allowing subsequent blinded multicenter evaluation of drugs with known positive, negative, or neutral inotropic effects. Accuracy ranged from 44% to 85% across the platform-cell configurations, indicating the need to refine test conditions. This was achieved by adopting approaches to reduce signal-to-noise ratio, reduce spontaneous beat rate to ≤ 1 Hz or enable chronic testing, improving accuracy to 85% for monolayers and 93% for EHTs. Contraction amplitude was a good predictor of negative inotropes across all the platform-cell configurations and of positive inotropes in the 3D EHTs. Although contraction- and relaxation-time provided confirmatory readouts forpositive inotropes in 3D EHTs, these parameters typically served as the primary source of predictivity in 2D. The reliance of these "secondary" parameters to inotropy in the 2D systems was not automatically intuitive and may be a quirk of hiPSC-CMs, hence require adaptations in interpreting the data from this model system. Of the platform-cell configurations, responses in EHTs aligned most closely to the free therapeutic plasma concentration. This study adds to the notion that hiPSC-CMs could add value to drug safety evaluation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.