{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:00:12Z","timestamp":1791378012456,"version":"4.3.2"},"reference-count":24,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIH R01s,HL114120,HL 131017,HL 149137,NIH U01 HL134764."],"award-info":[{"award-number":["NIH R01s,HL114120,HL 131017,HL 149137,NIH U01 HL134764."]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,22]]},"abstract":"<jats:p>The meager regenerative capacity of adult mammalian hearts appears to be driven by the proliferation of endogenous cardiomyocytes; thus, strategies targeting mechanisms of cardiomyocyte cell cycle regulation, such as the Hippo\/Yes-associated protein (Hippo\/Yap) pathway, could lead to the development of promising therapies for heart disease. The pharmacological product TT-10 increases cardiomyocyte proliferation by upregulating nuclear Yap levels. When intraperitoneal injections of TT-10 were administered to infarcted mouse hearts, the treatment promoted cardiomyocyte proliferation and was associated with declines in infarct size 1 week after administration, but cardiac function worsened at later time points. Here, we investigated whether encapsulating TT-10 into poly-lactic-co-glycolic acid nanoparticles (NPs) before administration could extend the duration of TT-10 delivery and improve the potency of TT-10 for myocardial repair. TT-10 was released from the TT-10\u2013loaded NPs for up to 4 weeks in vitro, and intramyocardial injections of TT-10\u2013delivered NPs stably improved cardiac function from week 1 to week 4 after administration to infarcted mouse hearts. TT-10\u2013delivered NP treatment was also associated with significantly smaller infarcts at week 4, with increases in cardiomyocyte proliferation and nuclear Yap abundance and with declines in cardiomyocyte apoptosis. Thus, NP-mediated delivery appears to enhance both the potency and durability of TT-10 treatment for myocardial repair.<\/jats:p>","DOI":"10.1172\/jci.insight.151987","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T14:01:06Z","timestamp":1634824866000},"source":"Crossref","is-referenced-by-count":21,"title":["TT-10\u2013loaded nanoparticles promote cardiomyocyte proliferation and cardiac repair in a mouse model of myocardial infarction"],"prefix":"10.1172","volume":"6","author":[{"given":"Wangping","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Alabama, Birmingham, USA."},{"name":"Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-2483","authenticated-orcid":true,"given":"Danielle","family":"Pretorius","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Alabama, Birmingham, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9217-5208","authenticated-orcid":true,"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Alabama, Birmingham, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-4775","authenticated-orcid":true,"given":"Yuji","family":"Nakada","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Alabama, Birmingham, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Alabama, Birmingham, USA."},{"name":"Department of Medicine and Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, 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