ArticlePloS one2016
Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes-a systematic review.Pflugers Archiv : European journal of physiology · 2019Pooled it
- Heart-on-a-chip and vasculature-on-a-chip platforms as models of cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Advanced in vitro cardiac models for drug evaluation: integration of organoids, engineered tissues, and microphysiological systems.Microsystems & nanoengineering · 2026Review
- Investigating PKD2 deficiency-associated cardiomyopathies using hESC-cardiomyocytes and bioengineered 3D ventricular cardiac tissue strips.Cell death & disease · 2026Article
- Human Cardiac Organoids: Advances and Prospects from Construction to Preclinical Drug Evaluation.Cells · 2025Review
- Generation and applications of cardiac spheroids.npj biomedical innovations · 2025Review
- Transformative Potential of Induced Pluripotent Stem Cells in Congenital Heart Disease Research and Treatment.Children (Basel, Switzerland) · 2025Review
- Modelling neurocardiac physiology and diseases using human pluripotent stem cells: current progress and future prospects.The Journal of physiology · 2025Review
- Three-Dimensional iPSC-Based In Vitro Cardiac Models for Biomedical and Pharmaceutical Research Applications.International journal of molecular sciences · 2024Review
- Progress of organoid platform in cardiovascular research.Bioactive materials · 2024Review
- Three-dimensional cardiac models: a pre-clinical testing platform.Biochemical Society transactions · 2024Review
- Article
- Microphysiological systems for human aging research.Aging cell · 2024Review
- Time-dependent effects of BRAF-V600E on cell cycling, metabolism, and function in engineered myocardium.Science advances · 2024Article
- hsa-miR-548v controls the viscoelastic properties of human cardiomyocytes and improves their relaxation rates.JCI insight · 2024Article
- Synthetic embryology of the human heart.Frontiers in cell and developmental biology · 2024Review
- Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers.Medicina (Kaunas, Lithuania) · 2023Review
- Advances in 3D Organoid Models for Stem Cell-Based Cardiac Regeneration.International journal of molecular sciences · 2023Review
- Increased length-dependent activation of human engineered heart tissue after chronic αAmerican journal of physiology. Heart and circulatory physiology · 2023Article
- Human cardiac organoids: A recent revolution in disease modeling and regenerative medicine.Journal of cardiovascular and thoracic research · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death that often goes undetected in the general population. HCM is also prevalent in patients with cardio-facio-cutaneous syndrome (CFCS), which is a genetic disorder characterized by aberrant signaling in the RAS/MAPK signaling cascade. Understanding the mechanisms of HCM development in such RASopathies may lead to novel therapeutic strategies, but relevant experimental models of the human condition are lacking. Therefore, the objective of this study was to develop the first 3D human engineered cardiac tissue (hECT) model of HCM. The hECTs were created using human cardiomyocytes obtained by directed differentiation of induced pluripotent stem cells derived from a patient with CFCS due to an activating BRAF mutation. The mutant myocytes were directly conjugated at a 3:1 ratio with a stromal cell population to create a tissue of defined composition. Compared to healthy patient control hECTs, BRAF-hECTs displayed a hypertrophic phenotype by culture day 6, with significantly increased tissue size, twitch force, and atrial natriuretic peptide (ANP) gene expression. Twitch characteristics reflected increased contraction and relaxation rates and shorter twitch duration in BRAF-hECTs, which also had a significantly higher maximum capture rate and lower excitation threshold during electrical pacing, consistent with a more arrhythmogenic substrate. By culture day 11, twitch force was no longer different between BRAF and wild-type hECTs, revealing a temporal aspect of disease modeling with tissue engineering. Principal component analysis identified diastolic force as a key factor that changed from day 6 to day 11, supported by a higher passive stiffness in day 11 BRAF-hECTs. In summary, human engineered cardiac tissues created from BRAF mutant cells recapitulated, for the first time, key aspects of the HCM phenotype, offering a new in vitro model for studying intrinsic mechanisms and screening new therapeutic approaches for this lethal form of heart disease.
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Registered trials
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