ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Cardiac Non-myocyte Cells Show Enhanced Pharmacological Function Suggestive of Contractile Maturity in Stem Cell Derived Cardiomyocyte Microtissues.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 122 citations in OpenAlex.
- Hydrogel platforms for 3D cardiac tissue engineering and fibrotic disease modelling.FEBS open bio · 2026Review
- Genotype-Dependent Effects of Mechanical Stretch and GATA4-Targeted Compound 3i-1262 in Cardiomyopathy Patient-Derived hiPSC-Cardiomyocytes.Basic & clinical pharmacology & toxicology · 2026Article
- Rhythms of growth: unveiling the mechanobiology behind heart maturation.The Journal of physiology · 2026Review
- Efficient multi-lineage cardiovascular differentiation of human pluripotent stem cells in animal serum-free conditions.Scientific reports · 2026Article
- Vascularized and Perfusable Human Heart-on-a-Chip Model Recapitulates Aspects of Myocardial Ischemia and Enables Analysis of Nanomedicine Delivery.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Integrative approaches in cardiac tissue engineering: Bridging cellular complexity to create accurate physiological models.iScience · 2025Review
- Discovering a predictive metabolic signature of drug-induced structural cardiotoxicity in cardiac microtissues.Archives of toxicology · 2025Article
- Modelling neurocardiac physiology and diseases using human pluripotent stem cells: current progress and future prospects.The Journal of physiology · 2025Review
- Applications of carbon dot-mediated cardiomyocyte maturation in regenerative medicine: a review.Nanomedicine (London, England) · 2025Review
- iPSC-Derived Cardiomyocytes as a Disease Model to Understand the Biology of Congenital Heart Defects.Cells · 2024Review
- Three-dimensional cardiac models: a pre-clinical testing platform.Biochemical Society transactions · 2024Review
- Vascularization of PEGylated fibrin hydrogels increases the proliferation of human iPSC-cardiomyocytes.Journal of biomedical materials research. Part A · 2024Article
- Vascularised cardiac spheroids-on-a-chip for testing the toxicity of therapeutics.Scientific reports · 2024Article
- Anticancer drugs and cardiotoxicity: the role of cardiomyocyte and non-cardiomyocyte cells.Frontiers in cardiovascular medicine · 2024Review
- FRESH™ 3D bioprinted cardiac tissue, a bioengineered platform forAPL bioengineering · 2023Article
- Mesothelial Cells Exhibit Characteristics of Perivascular Cells in an In Vitro Angiogenesis Assay.Cells · 2023Article
- Towards Improved HumanBiomedicines · 2023Review
- Three-Dimensional Cell Cultures: The Bridge between In Vitro and In Vivo Models.International journal of molecular sciences · 2023Review
- Beyond pharmaceuticals: Fit-for-purpose new approach methodologies for environmental cardiotoxicity testing.ALTEX · 2023Review
- Modelling the pathology and treatment of cardiac fibrosis in vascularised atrial and ventricular cardiac microtissues.Frontiers in cardiovascular medicine · 2023Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The immature phenotype of stem cell derived cardiomyocytes is a significant barrier to their use in translational medicine and pre-clinical in vitro drug toxicity and pharmacological analysis. Here we have assessed the contribution of non-myocyte cells on the contractile function of co-cultured human embryonic stem cell derived cardiomyocytes (hESC-CMs) in spheroid microtissue format. Microtissues were formed using a scaffold free 96-well cell suspension method from hESC-CM cultured alone (CM microtissues) or in combination with human primary cardiac microvascular endothelial cells and cardiac fibroblasts (CMEF microtissues). Contractility was characterized with fluorescence and video-based edge detection. CMEF microtissues displayed greater Ca(2+ )transient amplitudes, enhanced spontaneous contraction rate and remarkably enhanced contractile function in response to both positive and negative inotropic drugs, suggesting a more mature contractile phenotype than CM microtissues. In addition, for several drugs the enhanced contractile response was not apparent when endothelial cell or fibroblasts from a non-cardiac tissue were used as the ancillary cells. Further evidence of maturity for CMEF microtissues was shown with increased expression of genes that encode proteins critical in cardiac Ca(2+ )handling (S100A1), sarcomere assembly (telethonin/TCAP) and β-adrenergic receptor signalling. Our data shows that compared with single cell-type cardiomyocyte in vitro models, CMEF microtissues are superior at predicting the inotropic effects of drugs, demonstrating the critical contribution of cardiac non-myocyte cells in mediating functional cardiotoxicity.
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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.