{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T23:01:24Z","timestamp":1762642884561,"version":"3.41.2"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers myocardial recovery in a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery of xenogeneic hUCM-MSC as reperfusion-adjuvant therapy in a translational model of AMI in swine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a placebo-controlled trial, pot-belied pigs were randomly assigned to a sham-control group (vehicle-injection; <jats:italic>n<\/jats:italic>\u2009=\u20098), AMI\u2009+\u2009vehicle (<jats:italic>n<\/jats:italic>\u2009=\u200912) or AMI\u2009+\u2009IC-injection (<jats:italic>n<\/jats:italic>\u2009=\u200911) of 5\u2009\u00d7\u200910<jats:sup>5<\/jats:sup> hUCM-MSC\/Kg, within 30\u2005min of reperfusion. AMI was created percutaneously by balloon occlusion of the mid-LAD. Left-ventricular function was blindly evaluated at 8-weeks by invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship in skinned cardiomyocytes and gene expression analysis by RNA-sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As compared to vehicle, hUCM-MSC enhanced systolic function as shown by higher ejection fraction (65\u2009\u00b1\u20096% vs. 43\u2009\u00b1\u20094%; <jats:italic>p<\/jats:italic>\u2009=\u20090.0048), cardiac index (4.1\u2009\u00b1\u20090.4 vs. 3.1\u2009\u00b1\u20090.2\u2005L\/min\/m<jats:sup>2<\/jats:sup>; <jats:italic>p<\/jats:italic>\u2009=\u20090.0378), preload recruitable stroke work (75\u2009\u00b1\u200913 vs. 36\u2009\u00b1\u20094\u2005mmHg; <jats:italic>p<\/jats:italic>\u2009=\u20090.0256) and end-systolic elastance (2.8\u2009\u00b1\u20090.7 vs. 2.1\u2009\u00b1\u20090.4\u2005mmHg*m<jats:sup>2<\/jats:sup>\/ml; <jats:italic>p<\/jats:italic>\u2009=\u20090.0663). Infarct size was non-significantly lower in cell-treated animals (13.7\u2009\u00b1\u20092.2% vs. 15.9\u2009\u00b1\u20092.7%; \u0394\u2009=\u2009\u22122.2%; <jats:italic>p<\/jats:italic>\u2009=\u20090.23), as was interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium. Sarcomere active tension improved, and genes related to extracellular matrix remodelling (including MMP9, TIMP1 and PAI1), collagen fibril organization and glycosaminoglycan biosynthesis were downregulated in animals treated with hUCM-MSC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intracoronary transfer of xenogeneic hUCM-MSC shortly after reperfusion improved left-ventricular systolic function, which could not be explained by the observed extent of infarct size reduction alone. Combined contributions of favourable modification of myocardial interstitial fibrosis, matrix remodelling and enhanced cardiomyocyte contractility in the remote myocardium may provide mechanistic insight for the biological effect.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1186574","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T05:23:35Z","timestamp":1685942615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion"],"prefix":"10.3389","volume":"10","author":[{"given":"Lu\u00eds","family":"Raposo","sequence":"first","affiliation":[]},{"given":"Rui J.","family":"Cerqueira","sequence":"additional","affiliation":[]},{"given":"Sara","family":"Leite","sequence":"additional","affiliation":[]},{"given":"Liliana","family":"Moreira-Costa","sequence":"additional","affiliation":[]},{"given":"Tiago L.","family":"Laundos","sequence":"additional","affiliation":[]},{"given":"Joana O.","family":"Miranda","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Mendes-Ferreira","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o Almeida","family":"Coelho","sequence":"additional","affiliation":[]},{"given":"Rita N.","family":"Gomes","sequence":"additional","affiliation":[]},{"given":"Perp\u00e9tua","family":"Pinto-do-\u00d3","sequence":"additional","affiliation":[]},{"given":"Diana S.","family":"Nascimento","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9 P.","family":"Louren\u00e7o","sequence":"additional","affiliation":[]},{"given":"Nuno","family":"Cardim","sequence":"additional","affiliation":[]},{"given":"Adelino","family":"Leite-Moreira","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2023,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1093\/eurheartj\/ehr018","article-title":"Stem and progenitor cell-based therapy in ischaemic heart disease: promise, uncertainties, and challenges","volume":"32","author":"Tongers","year":"2011","journal-title":"Eur Hear J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1093\/eurheartj\/eht372","article-title":"Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis","volume":"35","author":"Delewi","year":"2014","journal-title":"Eur Hear J"},{"key":"B3","doi-asserted-by":"publisher","first-page":"CD006536","DOI":"10.1002\/14651858.CD006536.pub4","article-title":"Stem cell treatment for acute myocardial infarction","volume":"9","author":"Fisher","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1111\/j.1582-4934.2010.01231.x","article-title":"Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration","volume":"15","author":"Shao","year":"2011","journal-title":"J Cell Mol Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"100ra90","DOI":"10.1126\/scitranslmed.3002814","article-title":"Donor myocardial infarction impairs the therapeutic potential of bone marrow cells by an interleukin-1-mediated inflammatory response","volume":"3","author":"Wang","year":"2011","journal-title":"Sci Transl Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1161\/CIRCULATIONAHA.106.644518","article-title":"CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells","volume":"114","author":"Kawamoto","year":"2006","journal-title":"Circulation"},{"key":"B7","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. 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