{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T01:04:03Z","timestamp":1782954243239,"version":"3.54.5"},"reference-count":65,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770291"],"award-info":[{"award-number":["81770291"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>To investigate the role of self\u2010peripheral blood mesenchymal stem cell (PBMSC)\u2010derived exosomes (Exos) in enhancing renal sympathetic denervation (RD)\u2010mediated heart regeneration following myocardial infarction (MI) in a porcine model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pigs (ejection fraction [EF]\u00a0&lt;\u00a040% post\u2010MI) were randomised to early sham RD or RD. At 2 weeks post\u2010MI, autologous PBMSC\u2010Exos were collected. At 30 days post\u2010MI, pigs received either PBMSC\u2010Exos (2 \u00d7 10<jats:sup>13<\/jats:sup> particles) or phosphate\u2010buffered saline and were followed until 90 days. Another cohort underwent myocardial biopsy at 14 days post\u2010MI to assess PBMSC\u2010Exos effects on ischaemic cardiomyocyte (CM) reprogramming, followed by adeno\u2010associated viral therapy with miR\u2010141\u2010200\u2010429 sponges or negative control sponges to explore the role of miR\u2010141\u2010200\u2010429 clusters in reprogramming.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two weeks post\u2010MI, RD hearts showed increased Exos uptake and inhibited the sympathetic nervous system. By 90 days, the RD+Exos group had 11%\u201326% higher EF than single\u2010treatment groups (all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001), with improved survival and reduced fibrosis. Exos therapy enhanced RD effects by suppressing the renin\u2012angiotensin\u2012aldosterone system and transferring the miR\u2010141\u2010200\u2010429 cluster into ischaemic CMs. CMs from RD\u2010treated hearts cocultured with PBMSC\u2010Exos<jats:sup>RD<\/jats:sup> exhibited a more immature state, promoting reprogramming. \u03b2\u2010Catenin overexpression further enhanced PBMSC\u2010Exos<jats:sup>RD<\/jats:sup> effects, while miR\u2010141\u2010200\u2010429 inhibition blocked RD\u2010induced CM reprogramming and survival. Ultimately, PBMSC\u2010Exos<jats:sup>RD<\/jats:sup> reduced dickkopf\u20101 (Dkk1) expression and activated GSK3\u03b2 phosphorylation, thereby stimulating the Wnt\/\u03b2\u2010catenin pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PBMSC\u2010Exos<jats:sup>RD<\/jats:sup> enhances RD\u2010mediated cardiac repair through miR\u2010141\u2010200\u2010429 cluster\u2010dependent activation of the Wnt\/\u03b2\u2010catenin pathway, offering a novel therapeutic strategy for MI\u2010induced heart failure. Our findings unveil a novel therapeutic strategy, highlighting that RD maintains its efficacy and safety when integrated with complementary approaches over extended periods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Myocardial infarction triggers cardiomyocyte depletion and sympathetic overactivation, culminating in irreversible heart failure.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Renal denervation (RD) attenuates sympathetic signalling, modulating catecholamine\u2012B\u2010type natriuretic peptide (BNP) homeostasis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We newly demonstrate RD\u2010enhanced peripheral blood mesenchymal stem cell exosomal secretion enriched with miR\u2010141\u2010200\u2010429 clusters.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These exosomal miRNAs suppress dickkopf\u20101 (Dkk1), activating GSK3\u03b2\/Wnt\/\u03b2\u2010catenin signalling to enhance myocardial survival and regeneration.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our findings establish a combined therapeutic paradigm wherein RD maintains durable efficacy and safety alongside complementary interventions for heart failure management.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70475","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T09:42:49Z","timestamp":1757065369000},"source":"Crossref","is-referenced-by-count":3,"title":["Peripheral blood mesenchymal stem cell\u2010derived exosomes improve renal sympathetic denervation efficacy through \u03b2\u2010catenin\u2010mediated cardiac reprogramming"],"prefix":"10.1002","volume":"15","author":[{"given":"Lan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cardiology Guangzhou Red Cross Hospital of Ji\u2010Nan University  Guangzhou China"},{"name":"Department of Cardiology Dahua Hospital  Shanghai 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