ArticleTissue engineering. Part C, Methods2018
Development of In Vitro Drug-Induced Cardiotoxicity Assay by Using Three-Dimensional Cardiac Tissues Derived from Human Induced Pluripotent Stem Cells.
Article in Tissue engineering. Part C, Methods, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 103 citations in OpenAlex.
- Metabolic fatty acid substrates enhance the structural and mechanical performance of human-induced pluripotent stem cell-derived cardiomyocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Bioprinting High-Cell-Density Cardiac Tissue Constructs With Sustained Contractile Function.Advanced healthcare materials · 2026Article
- A humanized engineered heart tissue platform for cardiotoxicity assessment.Stem cell reports · 2026Article
- Microphysiological systems as an emerging in vitro approach for the evaluation of drug absorption, distribution, metabolism, and excretion and toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- The hanging-heart chip: A portable microfluidic device for high-throughput generation of contractile embryonic stem cell-derived cardiac spheroids.Bioengineering & translational medicine · 2025Article
- Maturation of pluripotent stem cell-derived cardiomyocytes: limitations and challenges from metabolic aspects.Stem cell research & therapy · 2024Review
- Gellan gum-gelatin based cardiac models support formation of cellular networks and functional cardiomyocytes.Cytotechnology · 2024Article
- Transcriptomic Approaches to Cardiomyocyte-Biomaterial Interactions: A Review.ACS biomaterials science & engineering · 2024Review
- Human induced pluripotent stem cell-derived closed-loop cardiac tissue for drug assessment.iScience · 2024Article
- A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications.Biomaterials · 2024Review
- Cardiac Organoids: A 3D Technology for Disease Modeling and Drug Screening.Current medicinal chemistry · 2024Review
- Establishment of a protocol to administer immunosuppressive drugs for iPS cell-derived cardiomyocyte patch transplantation in a rat myocardial infarction model.Scientific reports · 2023Article
- Dynamic mechanobiology of cardiac cells and tissues: Current status and future perspective.Biophysics reviews · 2023Review
- Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease.Nature communications · 2023Article
- Advances in the design, generation, and application of tissue-engineered myocardial equivalents.Frontiers in bioengineering and biotechnology · 2023Review
- Article
- Involvement of kallikrein-PAR2-proinflammatory pathway in severe trastuzumab-induced cardiotoxicity.Cancer science · 2022Article
- Functional human cell-based vascularised cardiac tissue model for biomedical research and testing.Scientific reports · 2022Article
- Microphysiological stem cell models of the human heart.Materials today. Bio · 2022Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An in vitro drug-induced cardiotoxicity assay is a critical step in drug discovery for clinical use. The use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is promising for this purpose. However, single hiPSC-CMs are limited in their ability to mimic native cardiac tissue structurally and functionally, and the generation of artificial cardiac tissue using hiPSC-CMs is an ongoing challenging. We therefore developed a new method of constructing three-dimensional (3D) artificial tissues in a short time by coating extracellular matrix (ECM) components on cell surfaces. We hypothesized that 3D cardiac tissues derived from hiPSC-CMs (3D-hiPSC-CT) could be used for an in vitro drug-induced cardiotoxicity assay. 3D-hiPSC-CT were generated by fibronectin and gelatin nanofilm coated single hiPSC-CMs. Histologically, 3D-hiPSC-CT exhibited a sarcomere structure in the myocytes and ECM proteins, such as fibronectin, collagen type I/III, and laminin. The administration of cytotoxic doxorubicin at 5.0 μM induced the release of lactate dehydrogenase, while that at 2.0 μM reduced the cell viability. E-4031, human ether-a-go-go related gene (hERG)-type potassium channel blocker, and isoproterenol induced significant changes both in the Ca transient parameters and contractile parameters in a dose-dependent manner. The 3D-hiPSC-CT exhibited doxorubicin-sensitive cytotoxicity and hERG channel blocker/isoproterenol-sensitive electrical activity in vitro, indicating its usefulness for drug-induced cardiotoxicity assays or drug screening systems for drug discovery.
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