What is the clinical evidence from this study?

Study design: Systematic Review. Population: Cardiac injury and heart failure. Intervention: Extracellular vesicles (EVs). Primary outcome: Mitochondrial dynamics, ROS accumulation, and cardiomyocyte survival.

November 5, 2025Cells16 citationsOpen Access

Targeting Mitochondrial Dynamics via EV Delivery in Regenerative Cardiology: Mechanistic and Therapeutic Perspectives

DSDhienda C. ShahannazCleveland Clinic TSTadahisa SugiuraAlbert Einstein College of Medicine BFBrandon E. FerrellAlbert Einstein College of Medicine

Key Result

Across 48 studies, extracellular vesicles modulated mitochondrial dynamics, restored membrane potential, reduced ROS accumulation, and improved cardiomyocyte survival.

Study Design

Type

Systematic Review

Structured PICO

Do extracellular vesicles delivering mitochondrial-targeted cargo improve mitochondrial dynamics and cardiomyocyte survival in preclinical models of cardiac injury?

Population

Systematic review of 48 original studies evaluating extracellular vesicles for mitochondrial modulation in regenerative cardiology.

Intervention

Extracellular vesicles (EVs) delivering mitochondrial-targeted cargo.

Outcome

Modulation of mitochondrial dynamics (fusion, fission, mitophagy, and biogenesis) and cardiomyocyte survival.surrogate

EV-mediated mitochondrial modulation shows promise for cardiac repair by improving mitochondrial dynamics and cardiomyocyte survival, though standardization is needed for clinical translation.

Limitations

Lack of standardized preparation and quantitative assessment methods
Need for harmonized protocols and deeper mechanistic understanding
Need for improved translational readiness

Abstract

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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