ArticleCirculation. Arrhythmia and electrophysiology2013
Mechanism-based facilitated maturation of human pluripotent stem cell-derived cardiomyocytes.
Article in Circulation. Arrhythmia and electrophysiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 178 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
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- Investigating PKD2 deficiency-associated cardiomyopathies using hESC-cardiomyocytes and bioengineered 3D ventricular cardiac tissue strips.Cell death & disease · 2026Article
- Large-scale synthetic data enable digital twins of human excitable cells.bioRxiv : the preprint server for biology · 2025Article
- Article
- Advancements in techniques for human iPSC-derived cardiomyocytes maturation: mechanical and electrical stimulation approaches.Biophysical reviews · 2025Review
- The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity.International journal of molecular sciences · 2024Review
- Advances in induced pluripotent stem cell-derived cardiac myocytes: technological breakthroughs, key discoveries and new applications.The Journal of physiology · 2024Review
- Synergistic effects of hormones on structural and functional maturation of cardiomyocytes and implications for heart regeneration.Cellular and molecular life sciences : CMLS · 2023Review
- Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes.Scientific reports · 2023Article
- Aging Model for Analyzing Drug-Induced Proarrhythmia Risks Using Cardiomyocytes Differentiated from Progeria-Patient-Derived Induced Pluripotent Stem Cells.International journal of molecular sciences · 2023Article
- Lysosomal CaPNAS nexus · 2023Article
- Single-cell RNA sequencing reveals maturation trajectory in human pluripotent stem cell-derived cardiomyocytes in engineered tissues.iScience · 2023Article
- Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy.Cell stem cell · 2023Article
- Multilayer control of cardiac electrophysiology by microRNAs.Journal of molecular and cellular cardiology · 2022Review
- Bioengineering Strategies to Create 3D Cardiac Constructs from Human Induced Pluripotent Stem Cells.Bioengineering (Basel, Switzerland) · 2022Review
- Xeno-Free Integrated Platform for Robust Production of Cardiomyocyte Sheets from hiPSCs.Stem cells international · 2022Article
- ESC working group on cardiac cellular electrophysiology position paper: relevance, opportunities, and limitations of experimental models for cardiac electrophysiology research.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2021Review
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Pathogenesis and drug response of iPSC-derived cardiomyocytes from two Brugada syndrome patients with different NaJournal of biomedical research · 2021Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundHuman embryonic stem cells (hESCs) can be efficiently and reproducibly directed into cardiomyocytes (CMs) using stage-specific induction protocols. However, their functional properties and suitability for clinical and other applications have not been evaluated. METHODS AND
resultsHere we showed that CMs derived from multiple pluripotent human stem cell lines (hESC: H1, HES2) and types (induced pluripotent stem cell) using different in vitro differentiation protocols (embryoid body formation, endodermal induction, directed differentiation) commonly displayed immature, proarrhythmic action potential properties such as high degree of automaticity, depolarized resting membrane potential, Phase 4- depolarization, and delayed after-depolarization. Among the panoply of sarcolemmal ionic currents investigated (I(Na)(+)/I(CaL)(+)/I(Kr)(+)/I(NCX)(+)/I(f)(+)/I(to)(+)/I(K1)(-)/I(Ks)(-)), we pinpointed the lack of the Kir2.1-encoded inwardly rectifying K(+) current (I(K1)) as the single mechanistic contributor to the observed immature electrophysiological properties in hESC-CMs. Forced expression of Kir2.1 in hESC-CMs led to robust expression of Ba(2+)-sensitive I(K1) and, more importantly, completely ablated all the proarrhythmic action potential traits, rendering the electrophysiological phenotype indistinguishable from the adult counterparts. These results provided the first link of a complex developmentally arrested phenotype to a major effector gene, and importantly, further led us to develop a bio-mimetic culturing strategy for enhancing maturation.
conclusionsBy providing the environmental cues that are missing in conventional culturing method, this approach did not require any genetic or pharmacological interventions. Our findings can facilitate clinical applications, drug discovery, and cardiotoxicity screening by improving the yield, safety, and efficacy of derived CMs.
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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.