Aug 2026· Journal of Controlled Release· pp.
115255
· 0 citations· 197 references
Medicine
TL;DR
This review systematically analyzes the key issues facing EV-based therapeutic strategies in their progression from experimental research to clinical application, providing a practical theoretical framework for EV-based myocardial repair therapies and clarifying the prospects for EVs in the treatment of MI.
Abstract
Myocardial infarction (MI) remains a major challenge in clinical practice, as the irreversible loss of cardiomyocytes and the limited repair capacity of the adult heart constrain cardiac repair. Traditional cell therapy once held great promise, but its clinical application has been constrained by issues such as low cell survival, immune rejection and procedural complexity. Against this background, extracellular vesicles (EVs) have attracted attention as a paracrine delivery strategy. By delivering bioactive cargo, including proteins, nucleic acids and lipids, EVs mediate intercellular communication and thereby support cardiac repair. This review focuses on the clinical potential of EVs, comparing the advantages, limitations and safety risks of EVs from different cellular origins, and places particular emphasis on engineered delivery strategies aimed at improving targeting, retention and therapeutic efficacy. In parallel, we examine the core barriers to clinical translation, including large scale manufacturing challenges, batch to batch consistency, storage stability, and regulatory and ethical issues; it is these barriers, rather than insufficient efficacy, that constitute the key bottleneck to the clinical application of EVs. Compared with existing reviews, this review, by emphasizing a clinical translation perspective, systematically analyzes the key issues facing EV-based therapeutic strategies in their progression from experimental research to clinical application, providing a practical theoretical framework for EV-based myocardial repair therapies and clarifying the prospects for EVs in the treatment of MI.
Current evidence on the roles of EVs in key pathological processes of HF, including inflammation, mitochondrial dysfunction, myocardial hypertrophy, fibrosis, apoptosis, and angiogenesis are summarized and their potential as circulating biomarkers for the diagnosis and prognosis are discussed.
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This review examines the full range of cell-based strategies studied to date, the clinical trial evidence, the barriers to progress, and what engineered vesicles, bioengineered tissue constructs, gene editing, and improved trial design might offer.