ArticleJACC. CardioOncology2021
Mitochondria-Rich Extracellular Vesicles Rescue Patient-Specific Cardiomyocytes From Doxorubicin Injury: Insights Into the SENECA Trial.
Article in JACC. CardioOncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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
62 citing papers in PubMed, 87 citations in OpenAlex.
- Sequential-RSC pharmaceutics · 2026Article
- Small Extracellular Vesicles in Cardioprotection, Cardiac Repair, and Regeneration: Cargo Mechanisms, Producer Cell Sources, and Translational Development.Biomedicines · 2026Review
- Review
- Tumor-derived apoptotic extracellular vesicles impede hepatocarcinoma progression by disrupting mitochondrial metabolism.Journal of translational medicine · 2026Article
- Eosinophil-derived apoptotic extracellular vesicles accelerate steatotic liver repair after ischemia/reperfusion injury through mitochondria-associated metabolic reprogramming.Journal of nanobiotechnology · 2026Article
- Mitochondria-containing large extracellular vesicles target mouse motor neurons upon intramuscular injection.Extracellular vesicle · 2026Article
- SPECTRA-based Detection of Drug-Induced Hepatotoxicity through Extracellular Vesicle Analysis.Sensors and actuators. B, Chemical · 2026Article
- Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.Open forum infectious diseases · 2026Article
- Mitochondria-Derived Vesicles and Mitochondrial Extracellular Vesicles in Health and Cardiovascular Disease.Circulation research · 2026Review
- Mitochondrial Transfer: From Bench to Bedside.Circulation research · 2026Review
- Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Understanding cardiovascular aging as a disorder of mitochondrial network.The journal of cardiovascular aging · 2026Article
- Nanomedicine-Based Strategies for Mitigating Chemo/Radiotherapy-Induced Cardiac Inflammation and Fibrosis.Cardiovascular toxicology · 2025Review
- Mitochondrial cargo quality determines the paracrine effects of extracellular vesicles derived from vascular endothelial cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Mitochondria-Enriched Extracellular Vesicles (EVs) for Cardiac Bioenergetics Restoration: A Scoping Review of Preclinical Mechanisms and Source-Specific Strategies.International journal of molecular sciences · 2025Article
- Review
- Mesenchymal stromal cell-mediated mitochondrial transfer unveils new frontiers in disease therapy.Stem cell research & therapy · 2025Review
- Extracellular Vesicles in Serum Carry Trop2 Protein as a Potential Molecular Indicator in Prostate Cancer.Journal of extracellular biology · 2025Article
- Therapeutic potential of human mesenchymal stromal cell-derived mitochondria in a rat model of surgical digestive fistula.Scientific reports · 2025Article
- Plasma Preparation Strategies for Extracellular Vesicle-Based Biomarkers in Metastatic Castration-Resistant Prostate Cancer.Journal of extracellular biology · 2025Article
2 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
20 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAnthracycline-induced cardiomyopathy (AIC) is a significant source of morbidity and mortality in cancer survivors. The role of mesenchymal stem cells (MSCs) in treating AIC was evaluated in the SENECA trial, a Phase 1 National Heart, Lung, and Blood Institute-sponsored study, but the mechanisms underpinning efficacy in human tissue need clarification.
objectivesThe purpose of this study was to perform an in vitro clinical trial evaluating the efficacy and putative mechanisms of SENECA trial-specific MSCs in treating doxorubicin (DOX) injury, using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iCMs) generated from SENECA patients.
methodsPatient-specific iCMs were injured with 1 μmol/L DOX for 24 hours, treated with extracellular vesicles (EVs) from MSCs by either coculture or direct incubation and then assessed for viability and markers of improved cellular physiology. MSC-derived EVs were separated into large extracellular vesicles (L-EVs) (>200 nm) and small EVs (<220nm) using a novel filtration system.
resultsiCMs cocultured with MSCs in a transwell system demonstrated improved iCM viability and attenuated apoptosis. L-EVs but not small EVs recapitulated this therapeutic effect. L-EVs were found to be enriched in mitochondria, which were shown to be taken up by iCMs. iCMs treated with L-EVs demonstrated improved contractility, reactive oxygen species production, ATP production, and mitochondrial biogenesis. Inhibiting L-EV mitochondrial function with 1-methyl-4-phenylpyridinium attenuated efficacy.
conclusionsL-EV-mediated mitochondrial transfer mitigates DOX injury in patient-specific iCMs. Although SENECA was not designed to test MSC efficacy, consistent tendencies toward a positive effect were observed across endpoints. Our results suggest a mechanism by which MSCs may improve cardiovascular performance in AIC independent of regeneration, which could inform future trial design evaluating the therapeutic potential of MSCs.
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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.