Key result
Extracellular vesicles carrying mitochondrial cargo restore mitochondrial function and improve cardiomyocyte survival during cardiac repair.
Why the study?
Mitochondrial dysfunction contributes to cardiac injury and heart failure, and extracellular vesicles have emerged as promising therapeutic agents, but evidence on how they modulate mitochondrial dynamics needed systematic mapping.
Does EV-mediated delivery of mitochondrial-targeted cargo improve mitochondrial dynamics and cellular repair in preclinical models of cardiac injury?
Systematic Review (n=48)
Does EV-mediated delivery of mitochondrial-targeted cargo improve mitochondrial dynamics and cellular repair in preclinical models of cardiac injury?
EV-mediated mitochondrial modulation is a highly promising preclinical strategy for myocardial repair, acting as an evolution beyond traditional stem cell therapies, though standardization is urgently needed for clinical translation.
Promising for mitochondrial-targeted EV therapies in cardiac injury models; extends preclinical evidence from 48 studies but standardization needed before trials.
Mitochondrial dysfunction is a key contributor to cardiac injury and heart failure, and extracellular vesicles (EVs) have emerged as promising therapeutic agents due to their ability to deliver mitochondrial-targeted cargo. This review systematically maps the evidence on how EVs modulate mitochondrial dynamics-including fusion, fission, mitophagy, and biogenesis-in regenerative cardiology. We comprehensively searched PubMed, Scopus, and Web of Science up to September 2025 for original studies. A total of 48 studies were included, with most utilizing EVs from mesenchymal stem cells, induced pluripotent stem cells, or cardiac progenitors. The review found that EV cargo influences key pathways such as DRP1 and MFN2, restores mitochondrial membrane potential, reduces ROS accumulation, and improves cardiomyocyte survival. While engineered EVs showed enhanced specificity, a lack of standardized preparation and quantitative assessment methods remains a significant challenge. We conclude that EV-mediated mitochondrial modulation is a promising strategy for cardiac repair, but the field needs harmonized protocols, deeper mechanistic understanding, and improved translational readiness to advance beyond preclinical research. The future of this research lies in integrating systems biology and precision targeting.
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Shahannaz et al. (2025) conducted a systematic review in Cardiac injury and heart failure (preclinical models) (n=48). Extracellular vesicles (EVs) delivering mitochondrial-targeted cargo was evaluated on Modulation of mitochondrial dynamics, membrane potential, ROS accumulation, and cardiomyocyte survival. Extracellular vesicles delivering mitochondrial-targeted cargo modulated key pathways such as DRP1 and MFN2, restored mitochondrial membrane potential, and improved cardiomyocyte survival in models of cardiac repair.
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