{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:34:41Z","timestamp":1784288081651,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T00:00:00Z","timestamp":1594166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["18PRE33960074"],"award-info":[{"award-number":["18PRE33960074"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Abnormal pulmonary vasculature directly affects the development and progression of congenital diaphragmatic hernia (CDH)\u2010associated pulmonary hypertension (PH). Though overarching structural and cellular changes in CDH\u2010affected pulmonary arteries have been documented, the precise role of the extracellular matrix (ECM) in the pulmonary artery (PA) pathophysiology remains undefined. Here, we quantify the structural, compositional, and mechanical CDH\u2010induced changes in the main and distal PA ECM and investigate the efficacy of mesenchymal stem cell\u2010derived extracellular vesicles (MSC\u2010EVs) as a therapy to ameliorate pathological vascular ECM changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant Sprague\u2010Dawley rodents were administered nitrofen to induce CDH\u2010affected pulmonary vasculature in the offspring. A portion of CDH\u2010affected pups was treated with intravenous infusion of MSC\u2010EVs (1\u2009\u00d7\u200910<jats:sup>10<\/jats:sup>\/mL) upon birth. A suite of histological, mechanical, and transmission electron microscopic analyses were utilized to characterize the PA ECM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CDH model main PA presented significantly altered characteristics\u2014including greater vessel thickness, greater lysyl oxidase (LOX) expression, and a relatively lower ultimate tensile strength of 13.6\u2009MPa compared to control tissue (25.1\u2009MPa), suggesting that CDH incurs ECM structural disorganization. MSC\u2010EV treatment demonstrated the potential to reverse CDH\u2010related changes, particularly through rapid inhibition of ECM remodeling enzymes (LOX and MMP\u20109). Additionally, MSC\u2010EV treatment bolstered structural aspects of the PA ECM and mitigated pathological disorganization as exhibited by increased medial wall thickness and stiffness that, while not significantly altered, trends away from CDH\u2010affected tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data demonstrate notable ECM remodeling in the CDH pulmonary vasculature, along with the capacity of MSC\u2010EVs to attenuate pathological ECM remodeling, identifying MSC\u2010EVs as a potentially efficacious therapeutic for CDH\u2010associated pulmonary hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.24914","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T13:18:40Z","timestamp":1592831920000},"page":"2402-2411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Extracellular vesicles influence the pulmonary arterial extracellular matrix in congenital diaphragmatic hernia"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4104-8356","authenticated-orcid":false,"given":"Madeline N.","family":"Monroe","sequence":"first","affiliation":[{"name":"Department of Bioengineering Rice University  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqin","family":"Zhaorigetu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery McGovern Medical School at the University of Texas Health Science Center and Children's Memorial Hermann Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4625-7413","authenticated-orcid":false,"given":"Vikas S.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery McGovern Medical School at the University of Texas Health Science Center and Children's Memorial Hermann Hospital  Houston 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of Texas Health Science Center and Children's Memorial Hermann Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Charles S.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery McGovern Medical School at the University of Texas Health Science Center and Children's Memorial Hermann Hospital  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Segura","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Pathology Texas Heart Institute  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis Maximilian","family":"Buja","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Pathology Texas Heart Institute  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn Jane","family":"Grande\u2010Allen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Rice University  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Harting","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery McGovern Medical School at the University of Texas Health Science Center and Children's Memorial Hermann Hospital  Houston 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