{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:08:37Z","timestamp":1789013317742,"version":"build-2803163510"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Intramyocardial injection of human pluripotent stem cell\u2010derived cardiomyocytes after myocardial infarction improves cardiac function in large animal models, but associated ventricular arrhythmias are a major safety concern. We hypothesized that transendocardial injection of human induced pluripotent stem cell\u2010derived committed cardiac progenitor cells (CCPs), combined with cardiac fibroblast\u2010derived extracellular matrix (cECM) to enhance cell retention, will generate cardiac tissue grafts improving contractility without triggering ventricular arrhythmias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Human induced pluripotent stem cells were differentiated using a bioreactor and small molecules to produce CCPs. Myocardial infarction was created using a coronary artery balloon occlusion and reperfusion model in Yucatan mini pigs. Four weeks later, transendocardial injections of CCPs+cECM (n=14), CCPs alone (n=14), cECM alone (n=4) or vehicle control (n=13) into the peri\u2010infarct region in a randomized cohort. Arrhythmias were evaluated using implanted event recorders. Cardiac magnetic resonance imaging, invasive pressure\u2010volume assessment, and immunohistology were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">A scalable biomanufacturing protocol was developed generating CCPs. Intramyocardial delivery of CCPs to post\u2010myocardial infarction porcine hearts resulted in engraftment and differentiation of CCPs, forming ventricular cardiomyocyte\u2010rich grafts. There was no significant difference in cardiac magnetic resonance imaging\u2010based measured cardiac volumes or function between control, CCP and CCP\u2009+\u2009cECM groups; however, pressure\u2010volume analysis showed the greatest dobutamine\u2010stimulated functional reserve in the CCP group. Delivery of CCPs did not result in tumors or ventricular arrhythmias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Transendocardial delivery of CCPs with or without cECM into postmyocardial infarction porcine hearts resulted in comparable human cardiomyocyte grafts that did not improve resting left ventricular function but CCPs did improve stress\u2010induced contractile reserve without triggering ventricular arrhythmias.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.050517","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T10:26:02Z","timestamp":1784975162000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Human Induced Pluripotent Stem Cell\u2010Derived Committed Cardiac Progenitors Generate Cardiac Tissue Grafts in a Swine Ischemic Cardiomyopathy Model Without Triggering Ventricular Arrhythmias"],"prefix":"10.1161","volume":"15","author":[{"given":"Amish N.","family":"Raval","sequence":"first","affiliation":[{"name":"University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]},{"name":"University of Wisconsin","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric G.","family":"Schmuck","sequence":"additional","affiliation":[{"name":"University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav","family":"Leonov","sequence":"additional","affiliation":[{"name":"University of Wisconsin School of Medicine and Public Health","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmita","family":"Roy","sequence":"additional","affiliation":[{"name":"University of Wisconsin School of Medicine 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