ArticlePloS one2015
Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis 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.
The trial behind it
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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure.Cardiovascular research · 2019Guideline
- Intramyocardial injection of allogeneic human induced pluripotent stem cell-derived cardiomyocytes in advanced ischemic heart failure: an early-stage randomized trial.Nature medicine · 2026Trial
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Senescence modulated cardiac repair with pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2026Article
- A self-locking conductive cardiac patch for immediate electrical integration with infarcted rat myocardium.Bioactive materials · 2026Article
- Progress and challenges in transplantation of human pluripotent stem cell derived cardiomyocytes for cardiac therapy.npj biomedical innovations · 2026Review
- Heart Regeneration for Clinical Application.Internal medicine (Tokyo, Japan) · 2026Review
- Key Steps in Murine Cardiac Engineering Validation: How Does It Affect the Efficiency of Cardiac Devices?BioMed research international · 2026Review
- Recent Advances of Pluripotent Stem Cell-Derived Cardiomyocytes for Regenerative Medicine.Metabolites · 2025Review
- Evidence for intermittent coupling of intramyocardial small, engineered heart tissues acutely implanted into rabbit myocardium.Cardiovascular research · 2025Article
- Hypoimmunogenic hPSC-derived cardiac organoids for immune evasion and heart repair.bioRxiv : the preprint server for biology · 2025Article
- Injectable biodegradable microcarriers for iPSC expansion and cardiomyocyte differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- CT-Visible Microspheres Enable Whole-Body In Vivo Tracking of Injectable Tissue Engineering Scaffolds.Advanced healthcare materials · 2024Article
- Review
- Micropatterned fibrin scaffolds increase cardiomyocyte alignment and contractility for the fabrication of engineered myocardial tissue.Journal of biomedical materials research. Part A · 2023Article
- Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts.Science advances · 2023Article
- Graft-host coupling changes can lead to engraftment arrhythmia: a computational study.The Journal of physiology · 2023Article
- Article
- Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft-Host Coupling.International journal of molecular sciences · 2023Article
- Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy.Cell stem cell · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC)-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle) delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz). Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they identify lack of electrical integration as a challenge to overcome in tissue engineered patches.
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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.