ArticleCirculation research2018
Exosomal microRNA-21-5p Mediates Mesenchymal Stem Cell Paracrine Effects on Human Cardiac Tissue Contractility.
Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- A systematic review on the role of MSC-derived exosomal miRNAs in the treatment of heart failure.Molecular biology reports · 2022Pooled it
- Human iPSC-EV-loaded nanofiber stent coatings accelerate vascular repair by enhancing EGFR/HIF-1α signaling and suppressing ROCK1-mediated remodeling.Materials today. Bio · 2026Article
- Enhancing the Scalable Manufacturing of Human Mesenchymal Stromal Cells in Dynamic Culture Using Bioactive Heparin/Collagen Layer-by-Layer Coated Microcarriers.Biotechnology journal · 2026Article
- MicroRNAs and SGLT2 inhibitors in cardiovascular disease: Shared pathways and emerging roles.Journal of molecular and cellular cardiology plus · 2026Review
- Biomimetic Bone Marrow Monocyte Membrane-Fused Extracellular Vesicles for Targeted Therapy of Myocardial Infarction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mapping the miRNA landscape of primitive macrophage extracellular vesicles highlights their pro-vasculogenic effects in engineered human cardiac tissue.APL bioengineering · 2026Article
- Epicardial extracellular vesicles modulate gene expression following ischemia-reperfusion injury in heart-on-a-chip.Materials today. Bio · 2026Article
- MiR-21-5p Protects Embryonic Growth and Heart Function During Developmental Hypoxia by Dampening HIF Responses and Altering Gene Expression.Comprehensive Physiology · 2026Article
- Cargo-driven extracellular vesicles as pharmaceutical nanocarriers: A pharmaceutics-oriented comparison of animal exosomes and plant-derived exosome-like nanoparticles.International journal of pharmaceutics: X · 2026Review
- Beyond Extracellular Vesicle (EV) Hype: Practical Solutions and Remaining Hurdles in EV Research, Manufacturing, and Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Natural polysaccharide-nucleic acid nanocomplex alleviates myocardial infarction by driving chronologically programmed macrophage polarization.Materials today. Bio · 2026Article
- The roles of the microtubule cytoskeletal network in cardiac mechanobiology.Journal of cell science · 2026Review
- M2 macrophage exosomes reverse heart failure post-myocardial infarction by suppressing type 1 interferon signaling in myeloid cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Mesenchymal Stem Cell-Derived Exosomes: A Tool for Heart Failure Repair - From Molecular Mechanisms to Clinical Potential.Journal of inflammation research · 2026Review
- The Promise of Exosomes in Cardiac Repair: When 'Best Things Come in Small Packages'.Journal of cellular and molecular medicine · 2025Review
- A Molecular Perspective on the Intricate Interplay Among Exosomes, Bioenergetic Metabolism, and the Pathogenesis of Diabetic Cardiomyopathy.Journal of cardiovascular translational research · 2025Review
- [Exosome-derived miR-1275 mediates IL-38 upregulation in lymphocytes to suppress lipopolysaccharide-induced apoptosis of myocardial cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Engineered EVs from LncEEF1G - overexpressing MSCs promote fibrotic liver regeneration by upregulating HGF release from hepatic stellate cells.Experimental & molecular medicine · 2025Article
- microRNAs shuttled by mesenchymal stromal cell-derived exosomes in coronary artery disease: A systematic review of preclinical studies.BioImpacts : BI · 2025Review
- Astragaloside promotes the secretion of MSC-derived exosomal miR-146a-5p by regulating TRAF6/NF-κB pathway to attenuate inflammation in high glucose-impaired endothelial cells.In vitro cellular & developmental biology. Animal · 2025Article
51 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
11 authors at 1 institution in 1 country.
Funding
Abstract
rationaleThe promising clinical benefits of delivering human mesenchymal stem cells (hMSCs) for treating heart disease warrant a better understanding of underlying mechanisms of action. hMSC exosomes increase myocardial contractility; however, the exosomal cargo responsible for these effects remains unresolved.
objectiveThis study aims to identify lead cardioactive hMSC exosomal microRNAs to provide a mechanistic basis for optimizing future stem cell-based cardiotherapies. METHODS AND
resultsIntegrating systems biology and human engineered cardiac tissue (hECT) technologies, partial least squares regression analysis of exosomal microRNA profiling data predicted microRNA-21-5p (miR-21-5p) levels positively correlate with contractile force and calcium handling gene expression responses in hECTs treated with conditioned media from multiple cell types. Furthermore, miR-21-5p levels were significantly elevated in hECTs treated with the exosome-enriched fraction of the hMSC secretome (hMSC-exo) versus untreated controls. This motivated experimentally testing the human-specific role of miR-21-5p in hMSC-exo-mediated increases of cardiac tissue contractility. Treating hECTs with miR-21-5p alone was sufficient to recapitulate effects observed with hMSC-exo on hECT developed force and expression of associated calcium handling genes (eg, SERCA2a and L-type calcium channel). Conversely, knockdown of miR-21-5p in hMSCs significantly diminished exosomal procontractile and associated calcium handling gene expression effects on hECTs. Western blots supported miR-21-5p effects on calcium handling gene expression at the protein level, corresponding to significantly increased calcium transient amplitude and decreased decay time constant in comparison to miR-scramble control. Mechanistically, cotreating with miR-21-5p and LY294002, a PI3K inhibitor, suppressed these effects. Finally, mathematical simulations predicted the translational capacity for miR-21-5p treatment to restore calcium handling in mature ischemic adult human cardiomyocytes.
conclusionsmiR-21-5p plays a key role in hMSC-exo-mediated effects on cardiac contractility and calcium handling, likely via PI3K signaling. These findings may open new avenues of research to harness the role of miR-21-5p in optimizing future stem cell-based cardiotherapies.
Indexed as
Identifiers
What OpenQuestion holds
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.