{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:16:07Z","timestamp":1791213367988,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Exosomes are extracellular vesicles 30 to 150\u2009nm in size, mediating the paracrine effects of mesenchymal stem cells (MSCs) and induced pluripotent stem cell\u2013derived cardiomyocytes (iCMs) when used to restore the injured myocardium. While both MSC\u2010 and iCM\u2010derived exosomes (MSC\u2010Exo, iCM\u2010Exo) improve cardiac function, their mechanisms of action remain incompletely understood. This study investigates the shared and distinct effects of iCM\u2010Exo and MSC\u2010Exo in a porcine ischemia\u2013reperfusion injury model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Female Yorkshire swine underwent proximal left anterior descending artery occlusion with a catheter balloon to induce ischemia\u2013reperfusion injury. Ten 500\u2010\u03bcL transendocardial injections\u00a0delivered a total of\u00a05\u00d710\n                      <jats:sup>11<\/jats:sup>\n                      iCM\u2010Exo or MSC\u2010Exo into the peri\u2010infarct region. Cardiac function was assessed via MRI at weeks 2 and 4, while transcriptomic sequencing of peri\u2010infarct tissue alongside exosomal cargo were performed to elucidate molecular drivers of exosome influenced, post ischemic modulation of gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cardiac MRI revealed that iCM\u2010Exo significantly improved left ventricular ejection fraction, myocardial viability, scar size, and ventricular remodeling compared with MSC\u2010Exo and PBS controls. Transcriptomic analysis revealed both shared and distinct gene expression patterns between the treatments. Shared pathways, including extracellular matrix remodeling and neurovascular integration, contributed to baseline cardiac improvement. Distinct pathways in iCM\u2010Exo treatment involved metabolic reorganization and cardiomyocyte\u2010specific processes, while MSC\u2010Exo emphasized structural stabilization and anti\u2010inflammatory responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">These findings highlight the complementary roles of iCM\u2010Exo and MSC\u2010Exo in myocardial repair with shared pathways contributing to baseline improvement and distinct pathways driving differences in efficacy. Future studies investigating the potential of combinatorial approaches may provide further insights into optimizing the therapeutic outcomes for patients with heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.037005","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:56:21Z","timestamp":1761216981000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Molecular Mechanisms of Exosomes From Human iPSC\u2010Cardiomyocytes and Mesenchymal Stem Cells in Restoring the Injured Myocardium"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-9192","authenticated-orcid":false,"given":"Eileen","family":"Tzng","sequence":"first","affiliation":[{"name":"Stanford University","place":["Stanford, 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