ArticleScientific reports2017
Modeling Atrial Fibrillation using Human Embryonic Stem Cell-Derived Atrial Tissue.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Towards chamber specific heart-on-a-chip for drug testing applications.Advanced drug delivery reviews · 2020Pooled it
- Sphingosine-1-phosphate receptor 1 signaling stimulates human pluripotent stem cell-derived cardiomyocyte differentiation and maturation.Experimental & molecular medicine · 2026Article
- Versatile hiPSC Models and Bioengineering Platforms for Investigation of Atrial Fibrosis and Fibrillation.Cells · 2026Review
- The role of iPSC research for insight into inherited arrhythmia conditions.Heart rhythm · 2025Review
- Article
- Application of human cardiac organoids in cardiovascular disease research.Frontiers in cell and developmental biology · 2025Review
- Identification of the optimal reference genes for atrial fibrillation model established by iPSC-derived atrial myocytes.BMC genomics · 2024Article
- Immune response caused by M1 macrophages elicits atrial fibrillation-like phenotypes in coculture model with isogenic hiPSC-derived cardiomyocytes.Stem cell research & therapy · 2024Article
- Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development.Cardiovascular research · 2023Article
- A critical role of retinoic acid concentration for the induction of a fully human-like atrial action potential phenotype in hiPSC-CM.Stem cell reports · 2023Article
- Utilizing human induced pluripotent stem cells to study atrial arrhythmias in the short QT syndrome.Journal of molecular and cellular cardiology · 2023Article
- Towards Improved HumanBiomedicines · 2023Review
- In Vitro Models for Improved Therapeutic Interventions in Atrial Fibrillation.Journal of personalized medicine · 2023Review
- Generation of cardiomyocytes from human-induced pluripotent stem cells resembling atrial cells with ability to respond to adrenoceptor agonists.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Human-Induced Pluripotent Stem Cell-Based Differentiation of Cardiomyocyte Subtypes for Drug Discovery and Cell Therapy.Handbook of experimental pharmacology · 2023Article
- Modeling the human heart ex vivo-current possibilities and strive for future applications.Journal of tissue engineering and regenerative medicine · 2022Review
- An iPS-derived in vitro model of human atrial conduction.Physiological reports · 2022Article
- Improved Atrial Differentiation of Human Pluripotent Stem Cells by Activation of Retinoic Acid Receptor Alpha (RARα).Journal of personalized medicine · 2022Article
- Conditional immortalization of human atrial myocytes for the generation of in vitro models of atrial fibrillation.Nature biomedical engineering · 2022Article
- Bioengineering approaches to treat the failing heart: from cell biology to 3D printing.Nature reviews. Cardiology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Since current experimental models of Atrial Fibrillation (AF) have significant limitations, we used human embryonic stem cells (hESCs) to generate an atrial-specific tissue model of AF for pharmacologic testing. We generated atrial-like cardiomyocytes (CMs) from hESCs which preferentially expressed atrial-specific genes, and had shorter action potential (AP) durations compared to ventricular-like CMs. We then generated confluent atrial-like CM sheets and interrogated them using optical mapping techniques. Atrial-like CM sheets (~1 cm in diameter) showed uniform AP propagation, and rapid re-entrant rotor patterns, as seen in AF could be induced. Anti-arrhythmic drugs were tested on single atrial-like CMs and cell sheets. Flecainide profoundly slowed upstroke velocity without affecting AP duration, leading to reduced conduction velocities (CVs), curvatures and cycle lengths of rotors, consistent with increased rotor organization and expansion. By contrast, consistent with block of rapid delayed rectifier K+ currents (Ikr) and AP prolongation in isolated atrial-like CMs, dofetilide prolonged APs and reduced cycle lengths of rotors in cell sheets without affecting CV. In conclusion, using our hESC-derived atrial CM preparations, we demonstrate that flecainide and dofetilide modulate reentrant arrhythmogenic rotor activation patterns in a manner that helps explain their efficacy in treating and preventing AF.
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