{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T05:03:33Z","timestamp":1779771813429,"version":"3.53.1"},"reference-count":137,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cardiovascular diseases remain the leading cause of mortality in developed countries. Among these conditions, acute myocardial infarction (AMI) is associated with particularly high rates of cardiac morbidity and mortality. Cardiac development in mammals is primarily dependent on cardiomyocyte (CM) proliferation during embryonic and early postnatal stages. However, following birth, the proliferative capacity of CMs declines markedly, with only limited cellular renewal occurring during adult life in response to pathological injury. Consequently, the irreversible loss of functional cardiomyocytes and the subsequent formation of fibrotic scar tissue frequently lead to persistent cardiac dysfunction and progressive impairment of cardiac physiology. Cardiomyocyte self-renewal is a tightly regulated process involving multiple molecular pathways. Among factors implicated in this regulation, microRNAs (miRNAs) have emerged as key modulators coordinating both cardiac development and tissue repair mechanisms. In this context, extracellular vesicles (EVs) have attracted considerable interest as potential modulators of these regenerative processes. In particular, mesenchymal stromal cells (MSCs) represent a promising therapeutic platform due to their immunomodulatory and anti-fibrotic properties demonstrated across multiple in vitro and in vivo models. Furthermore, the therapeutic potential of MSC-derived EVs can be enhanced through bioengineering approaches aimed at improving targeted molecular delivery. In this review, we summarize recent advances in the development and application of EV-based therapeutic strategies, with particular emphasis on their potential use as advanced therapy medicinal products (ATMPs) for cardiovascular regeneration and repair.<\/jats:p>","DOI":"10.3390\/cells15100900","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:06:26Z","timestamp":1779696386000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles in Cardiac Repair Approaches: Implications for In Vitro Heart Models and Potential ATMP Development"],"prefix":"10.3390","volume":"15","author":[{"given":"Simona","family":"Di Stefani","sequence":"first","affiliation":[{"name":"IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via E. Tricomi 5, 90127 Palermo, Italy"},{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Cimino","sequence":"additional","affiliation":[{"name":"IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via E. Tricomi 5, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4324-5097","authenticated-orcid":false,"given":"Rosaria","family":"Tinnirello","sequence":"additional","affiliation":[{"name":"IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via E. Tricomi 5, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina Maria","family":"Cocco","sequence":"additional","affiliation":[{"name":"IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via E. Tricomi 5, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9318-6606","authenticated-orcid":false,"given":"Cinzia Maria","family":"Chinnici","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Unit, Ri.MED Foundation, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6957-9861","authenticated-orcid":false,"given":"Giandomenico","family":"Amico","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Unit, Ri.MED Foundation, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4132-1260","authenticated-orcid":false,"given":"Valentina","family":"Di Felice","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5109-2070","authenticated-orcid":false,"given":"Filippo","family":"Macaluso","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-4505","authenticated-orcid":false,"given":"Bruno","family":"Douradinha","sequence":"additional","affiliation":[{"name":"OneCapsule, Marousi, 15126 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4460-9494","authenticated-orcid":false,"given":"Paolo","family":"Di Nardo","sequence":"additional","affiliation":[{"name":"Interdepartmental Center for Regenerative Medicine (CIMER), University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7710-4735","authenticated-orcid":false,"given":"Gioacchin","family":"Iannolo","sequence":"additional","affiliation":[{"name":"IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via E. Tricomi 5, 90127 Palermo, Italy"},{"name":"Department of Medicine and Surgery, Universit\u00e0 degli Studi di Enna \u201cKore\u201d, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e275","DOI":"10.1161\/CIR.0000000000001412","article-title":"2026 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association","volume":"153","author":"Palaniappan","year":"2026","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.5334\/gh.1538","article-title":"Quality of Life Assessment in Heart Failure Patients: Insights from a Low- to Middle-Income Country","volume":"21","author":"Khan","year":"2026","journal-title":"Glob. 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