ArticleToxicological sciences : an official journal of the Society of Toxicology2017
Blinded Contractility Analysis in hiPSC-Cardiomyocytes in Engineered Heart Tissue Format: Comparison With Human Atrial Trabeculae.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Towards chamber specific heart-on-a-chip for drug testing applications.Advanced drug delivery reviews · 2020Pooled it
- Electromechanical modelling and simulation of human-induced pluripotent stem cell-derived cardiomyocytes predict drug-induced contractility effects.The Journal of physiology · 2026Article
- Positive inotropic effects of serotonin in atrial EHT: further proof for an atrial phenotype?Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Induction of cardiac alternans in human iPS-derived cardiomyocytes through β-adrenergic receptor stimulation.Physiological reports · 2024Article
- iPSC-cardiomyocytes in the preclinical prediction of candidate pharmaceutical toxicity.Frontiers in pharmacology · 2024Review
- CRISPRi gene modulation and all-optical electrophysiology in post-differentiated human iPSC-cardiomyocytes.Communications biology · 2023Article
- A Platform for Assessing Cellular Contractile Function Based on Magnetic Manipulation of Magnetoresponsive Hydrogel Films.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi.Nature communications · 2023Article
- CRISPRi Gene Modulation and All-Optical Electrophysiology in Post-Differentiated Human iPSC-Cardiomyocytes.bioRxiv : the preprint server for biology · 2023Article
- Reproducibility of drug-induced effects on the contractility of an engineered heart tissue derived from human pluripotent stem cells.Frontiers in pharmacology · 2023Article
- Human induced pluripotent stem cell-derived cardiomyocytes as an electrophysiological model: Opportunities and challenges-The Hamburg perspective.Frontiers in physiology · 2023Review
- Challenges and opportunities for the next generation of cardiovascular tissue engineering.Nature methods · 2022Review
- Validating the Arrhythmogenic Potential of High-, Intermediate-, and Low-Risk Drugs in a Human-Induced Pluripotent Stem Cell-Derived Cardiac Microphysiological System.ACS pharmacology & translational science · 2022Article
- A Change of Heart: Human Cardiac Tissue Engineering as a Platform for Drug Development.Current cardiology reports · 2022Review
- Direct Contraction Force Measurements of Engineered Cardiac Tissue Constructs With Inotropic Drug Exposure.Frontiers in pharmacology · 2022Article
- Action potential variability in human pluripotent stem cell-derived cardiomyocytes obtained from healthy donors.Frontiers in physiology · 2022Article
- Acute effects of cardiac contractility modulation on human induced pluripotent stem cell-derived cardiomyocytes.Physiological reports · 2021Article
- Translational investigation of electrophysiology in hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology · 2021Article
- Depressed β-adrenergic inotropic responsiveness and intracellular calcium handling abnormalities in Duchenne Muscular Dystrophy patients' induced pluripotent stem cell-derived cardiomyocytes.Journal of cellular and molecular medicine · 2021Article
- Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects.Experimental biology and medicine (Maywood, N.J.) · 2021Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) may serve as a new assay for drug testing in a human context, but their validity particularly for the evaluation of inotropic drug effects remains unclear. In this blinded analysis, we compared the effects of 10 indicator compounds with known inotropic effects in electrically stimulated (1.5 Hz) hiPSC-CM-derived 3-dimensional engineered heart tissue (EHT) and human atrial trabeculae (hAT). Human EHTs were prepared from iCell hiPSC-CM, hAT obtained at routine heart surgery. Mean intra-batch variation coefficient in baseline force measurement was 17% for EHT and 49% for hAT. The PDE-inhibitor milrinone did not affect EHT contraction force, but increased force in hAT. Citalopram (selective serotonin reuptake inhibitor), nifedipine (LTCC-blocker) and lidocaine (Na+ channel-blocker) had negative inotropic effects on EHT and hAT. Formoterol (beta-2 agonist) had positive lusitropic but no inotropic effect in EHT, and positive clinotropic, lusitropic, and inotropic effects in hAT. Tacrolimus (calcineurin-inhibitor) had a negative inotropic effect in EHTs, but no effect in hAT. Digoxin (Na+-K+-ATPase-inhibitor) showed a positive inotropic effect only in EHTs, but no effect in hAT probably due to short incubation time. Ryanodine (ryanodine receptor-inhibitor) reduced contraction force in both models. Rolipram and acetylsalicylic acid showed noninterpretable results in hAT. Contraction amplitude and kinetics were more stable over time and less variable in hiPSC-EHTs than hAT. HiPSC-EHT faithfully detected cAMP-dependent and -independent positive and negative inotropic effects, but limited beta-2 adrenergic or PDE3 effects, compatible with an immature CM phenotype.
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Registered trials
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