{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:46:15Z","timestamp":1792622775438,"version":"4.5.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["VGHKS110-063"],"award-info":[{"award-number":["VGHKS110-063"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["VGHKS110-077"],"award-info":[{"award-number":["VGHKS110-077"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["VGHKS110-078"],"award-info":[{"award-number":["VGHKS110-078"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["108-2314-B-075B-009"],"award-info":[{"award-number":["108-2314-B-075B-009"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"publisher","award":["108-2314-B-075B-007-MY2"],"award-info":[{"award-number":["108-2314-B-075B-007-MY2"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007354","name":"Yen Tjing Ling Medical Foundation","doi-asserted-by":"publisher","award":["CI-111-26"],"award-info":[{"award-number":["CI-111-26"]}],"id":[{"id":"10.13039\/501100007354","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared with the induced pluripotent stem cells (iPSCs). Moreover, the exact mechanism is not known.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>In this study, we used murine iPSCs generated from mouse embryonic fibroblasts with triple factor (Oct4, Klf4, and Sox2) transduction to determine the efficacy and action mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension. Both early and late iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats. Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1\u03b1 and P21-activated kinase 1\/AKT\/Runx2 pathways.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>IPSC-Exo are effective at reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvad185","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T20:58:42Z","timestamp":1705957122000},"page":"203-214","source":"Crossref","is-referenced-by-count":21,"title":["Induced pluripotent stem cell\u2013derived exosomes attenuate vascular remodelling in pulmonary arterial hypertension by targeting HIF-1\u03b1 and Runx2"],"prefix":"10.1093","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-6682","authenticated-orcid":false,"given":"Pei-Ling","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Medical Education and Research, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan"},{"name":"Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Chang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Tzu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Bin","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Hung","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Chang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ci","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Kaohsiung Veterans General Hospital , Kaohsiung , 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