{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:17:25Z","timestamp":1789600645713,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by elevated pulmonary vascular resistance, leading to right ventricular (RV) hypertrophy and eventual heart failure. Although current therapies provide symptomatic relief, they offer limited efficacy in reversing the underlying vascular remodeling. In this preclinical study, we investigated the therapeutic potential of induced pluripotent stem cell\u2010derived conditioned medium (iPSC\u2010CM) in a monocrotaline (MCT)\u2010induced rat model of PAH, employing both prophylactic and therapeutic administration strategies. iPSC\u2010CM treatment significantly reduced right ventricular systolic pressure (RVSP) and mitigated RV hypertrophy compared to MCT\u2010only controls. Histological analyses revealed attenuated pulmonary arterial wall thickening and muscularization. At the molecular level, iPSC\u2010CM downregulated the expression of hypoxia\u2010inducible factor 1\u2010alpha (HIF\u20101\u03b1) and platelet\u2010derived growth factor\u2010BB (PDGF\u2010BB) in lung tissues, and modulated oxidative stress by decreasing NADPH oxidase 1 (Nox1) and increasing superoxide dismutase 1 (SOD1) levels. In vitro, iPSC\u2010CM suppressed the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) under hypoxic and PDGF\u2010BB\u2010stimulated conditions. These findings suggest that iPSC\u2010CM targets key pathogenic pathways involved in vascular remodeling and redox imbalance in PAH. Together, these findings support iPSC\u2010CM as a promising acellular approach for targeting vascular remodeling and oxidative stress in PAH, warranting further investigation toward clinical translation.<\/jats:p>","DOI":"10.1002\/jcp.70085","type":"journal-article","created":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T10:14:41Z","timestamp":1755425681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IPSC\u2010Derived Conditioned Medium Reduces Oxidative Stress and Vascular Remodeling in Rat Models of Pulmonary Arterial Hypertension"],"prefix":"10.1002","volume":"240","author":[{"given":"Chin\u2010Chang","family":"Cheng","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine Pingtung Veterans General Hospital Pingtung Taiwan"},{"name":"Department of Medicine, School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan"},{"name":"Department of Physical Therapy Fooyin University Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee\u2010Fen","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Care Chang Gung University of Science and Technology Chiayi Taiwan"},{"name":"Chronic Disease and Health Promotion Research Center Chang Gung University of Science and Technology Chiayi Taiwan"},{"name":"Division of Neurosurgery, Department of Surgery Chang Gung Memorial Hospital Chiayi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsien\u2010Hui","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pharmacy &amp; 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