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Synthetic mRNAs offer design flexibility and represent a modality particularly suitable for such approaches. To investigate this, five genes (\n                    <jats:italic>Hgf<\/jats:italic>\n                    ,\n                    <jats:italic>Igf1<\/jats:italic>\n                    ,\n                    <jats:italic>Pdgfb<\/jats:italic>\n                    ,\n                    <jats:italic>Cxcl12<\/jats:italic>\n                    , and\n                    <jats:italic>Tgf\u03b21<\/jats:italic>\n                    ) were selected from a model in which extracellular vesicles secreted by human iPSC\u2010derived cardiomyocytes restored cardiac function. Synthetic mRNAs encoding these genes were delivered via polyplex nanomicelles by direct myocardial administration in mice with MI\u2010induced heart failure. Nanomicelles have been shown to provide stable encapsulation, enhanced local expression, and prolonged persistence. This treatment promoted angiogenesis via the PI3K\u2013Akt\u2013ETV4 axis, suppressed fibrosis via inhibition of the JNK\/FOXO3 pathway, and enhanced repair by activating ERK signaling, together yielding multifaceted benefits, including tissue regeneration, improved contractility, and extended survival. These findings establish the therapeutic potential of multigene mRNA cocktail therapy for post\u2010MI heart failure and mark an important step toward developing new interventions for diseases characterized by complex remodeling.\n                  <\/jats:p>","DOI":"10.1002\/smsc.202500521","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T18:49:57Z","timestamp":1779562197000},"source":"Crossref","is-referenced-by-count":2,"title":["Nanomicelle\u2010Based Multi\u2010mRNA Delivery Promotes Cardiac Repair After Myocardial Infarction"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6080-2166","authenticated-orcid":false,"given":"Kazuma","family":"Handa","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery The University of Osaka Graduate School of Medicine  Osaka 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