ArticleEuropean heart journal2018
CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy.
Article in European heart journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
150 citing papers in PubMed, 2 syntheses or guidelines pooled it, 244 citations in OpenAlex.
- Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization.Expert opinion on drug metabolism & toxicology · 2021Pooled it
- Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes-a systematic review.Pflugers Archiv : European journal of physiology · 2019Pooled it
- Human iPSC-derived 3D cardiac models for cardiomyopathies: organoids, spheroids, and engineered heart tissues as translational platforms.Stem cells (Dayton, Ohio) · 2026Review
- Efficient multi-lineage cardiovascular differentiation of human pluripotent stem cells in animal serum-free conditions.Scientific reports · 2026Article
- Generation of biologically responsive colon-like intestinal tissue patches from human induced pluripotent stem cells using a rapid co-differentiation platform.Stem cell research & therapy · 2026Article
- Simtuzumab Attenuates Loxl2-Mediated Extracellular Matrix Remodeling and Preserves Cardiac Function inCirculation. Heart failure · 2026Article
- Heart Failure in the Molecular Era: Redefining Our Understanding of Disease Mechanisms and Perspectives.Biomedicines · 2026Review
- High-Throughput Methods for Variant Functional Assessment in Cardiac Disease.Circulation. Genomic and precision medicine · 2026Review
- Effects of Ranolazine on Vascular Adrenergic Receptors in Rabbit Aorta.International journal of medical sciences · 2026Article
- Targeting SRPK3 Attenuates Cardiac Hypertrophy and Heart Failure by Improving Mitochondrial Bioenergetics through mRNA Splicing and Decay.Research (Washington, D.C.) · 2026Article
- Early Cytoskeletal Remodeling Drives Hypertrophic Cardiomyopathy Pathogenesis inJournal of cardiovascular development and disease · 2025Article
- Metabolic cardiomyopathies: untangling clinical heterogeneity with human stem-cell derived models.EMBO molecular medicine · 2025Review
- Hypertrophic cardiomyopathy mutations Y115H and E497D disrupt the folded-back state of human β-cardiac myosin allosterically.Nature communications · 2025Article
- AAV-mediated overexpression of CPT1B protects from cardiac hypertrophy and heart failure in a murine pressure overload model.Basic research in cardiology · 2025Article
- Current status and new horizons in stem cell therapy in cardiovascular regenerative medicine (CaVaReM): an update.European journal of medical research · 2025Review
- Genetic architecture of hypertrophic cardiomyopathy in individuals of Chinese and United Kingdom ancestry.Precision clinical medicine · 2025Article
- Biomimetic Model for Electromagnetic Modulation of Cardiovascular Cellular Interactions On-Chip.ACS applied bio materials · 2025Article
- Review
- Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy.International journal of molecular sciences · 2025Review
- Cardiac Tissue Engineering for Translational Cardiology: From In Vitro Models to Regenerative Therapies.Bioengineering (Basel, Switzerland) · 2025Review
90 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Aims: Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening and heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardiomyocytes (hPSC-CM) for their validity to model, and add clarity to, HCM. Methods and results: CRISPR/Cas9 editing produced 11 variants of the HCM-causing mutation c.C9123T-MYH7 [(p.R453C-β-myosin heavy chain (MHC)] in 3 independent hPSC lines. Isogenic sets were differentiated to hPSC-CMs for high-throughput, non-subjective molecular and functional assessment using 12 approaches in 2D monolayers and/or 3D engineered heart tissues. Although immature, edited hPSC-CMs exhibited the main hallmarks of HCM (hypertrophy, multi-nucleation, hypertrophic marker expression, sarcomeric disarray). Functional evaluation supported the energy depletion model due to higher metabolic respiration activity, accompanied by abnormalities in calcium handling, arrhythmias, and contraction force. Partial phenotypic rescue was achieved with ranolazine but not omecamtiv mecarbil, while RNAseq highlighted potentially novel molecular targets. Conclusion: Our holistic and comprehensive approach showed that energy depletion affected core cardiomyocyte functionality. The engineered R453C-βMHC-mutation triggered compensatory responses in hPSC-CMs, causing increased ATP production and αMHC to energy-efficient βMHC switching. We showed that pharmacological rescue of arrhythmias was possible, while MHY7: MYH6 and mutant: wild-type MYH7 ratios may be diagnostic, and previously undescribed lncRNAs and gene modifiers are suggestive of new mechanisms.
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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.