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This function has positioned EVs as promising cell-free therapeutic agents with the potential to transform modern medicine. Stem and progenitor cells naturally release EVs that can replicate many of the therapeutic effects of cell transplantation, while avoiding the challenges associated with administering living cells. EVs derived from various cell sources\u2014including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, stromal cells, cardiac progenitor cells, and endothelial progenitor cells\u2014have shown therapeutic efficacy in preclinical models of ischemic heart disease. EVs\u2019 translation into human trials in cardiac therapy has lagged behind, however, largely due to challenges related to EV production standardization, regulatory frameworks, and the demonstration of reproducible efficacy in human subjects. Nevertheless, recent milestones have been achieved with the successful completion of the phase I EV-AMI trial (Safety Evaluation of Intracoronary Infusion of EVs in Patients with Acute Myocardial Infarction, NCT04327635) and the enrollment of the first patient in the phase I SECRET-HF trial (Treatment of Non-ischemic Cardiomyopathies by Intravenous Extracellular Vesicles of Cardiovascular Progenitor Cells, NCT05774509). This concise review outlines the evolution of EVs from basic biological discovery to innovative therapeutic platforms, with particular emphasis on their potential applications in acute myocardial infarction. Remaining challenges for clinical translation, including manufacturing and regulatory hurdles, will also be discussed.<\/jats:p>","DOI":"10.1093\/stmcls\/sxag022","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:46:14Z","timestamp":1776858374000},"source":"Crossref","is-referenced-by-count":0,"title":["From bench to bedside: stem and progenitor cell-derived extracellular vesicles in cardiac therapy"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-1173","authenticated-orcid":false,"given":"Carolina","family":"Balbi","sequence":"first","affiliation":[{"name":"Center for Molecular Cardiology, University of Zurich , Schlieren 8952,","place":["Switzerland"]},{"name":"Department of Internal Medicine, Cantonal Hospital Baden , Baden 5404,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia 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