{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:40:16Z","timestamp":1786390816238,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001779","name":"Monash University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001779","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited therapeutic options. This study compared the therapeutic effects of bone marrow mesenchymal stem cell\u2010derived extracellular vesicles (BM\u2010MSC\u2010EVs) with an IPF treatment, pirfenidone (PFD), in mature adult mice with established pulmonary fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Nine to 10\u2010month old male and female C57BL\/6 mice received an intranasal instillation of bleomycin (BLM) or saline on Days 0 and 7. Sub\u2010groups of BLM\u2010injured mice (n\u2009=\u200910 per group) were left untreated until Day 21 (d21) or d28 post\u2010injury, or received an intranasal administration of BM\u2010MSC\u2010EVs (d21), once\u2010daily oral PFD treatment (d21 to d27), or both treatments combined. Measures of lung compliance, inflammation and fibrosis were assessed at d28.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      BLM\u2010injured male and female mice had increased lung inflammation and interstitial transforming growth factor (TGF\u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      1), myofibroblast and extracellular matrix (ECM) accumulation, but reduced matrix metalloproteinase (MMP 9) activity and MMP9:TIMP\u20101 ratios at d21. These end\u2010points were maintained at d28 in male mice but were resolved in female mice. BM\u2010MSC\u2010EVs alone or combined with PFD attenuated or significantly reduced the lung inflammation and fibrosis\u2010related end\u2010points in male mice and promoted lung MMP\u20109 activity in both sexes. In comparison, PFD alone partially but significantly reduced fibrosis progression but did not affect MMP or TIMP levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>BM\u2010MSC\u2010EVs exerted anti\u2010fibrotic effects in male mice, which were maintained with PFD co\u2010administration. Treatment outcomes remained inconclusive in female mice. These findings highlight how ageing and sex influence therapeutic responses of EV\u2010based therapies for IPF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70539","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T01:22:39Z","timestamp":1781745759000},"page":"5423-5439","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic targeting of bleomycin\u2010induced pulmonary fibrosis by human bone marrow mesenchymal stem cell\u2010derived extracellular vesicles and\/or pirfenidone: Impact of sex in mature adult mice"],"prefix":"10.1111","volume":"183","author":[{"given":"Jennie S.","family":"Charoenphannathon","sequence":"first","affiliation":[{"name":"Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Pharmacology Monash University  Clayton Victoria 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