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Extracellular vesicles (EVs), particularly mesenchymal stem cell\u2010derived EVs, have shown therapeutic potential in sepsis\u2010related organ dysfunction by transferring RNAs and proteins. However, their clinical use is limited by low efficacy and yield. To address this, 3D\u2010cultured MSCs (3D\u2010MSCs) are generated using MicroTissues 3D Petri Dish. These 3D\u2010MSCs demonstrate improved protection and proliferation of MLE\u201012 cells in vitro. Mechanistic studies are conducted to explore the enhanced protective effects of 3D\u2010MSCs derived EVs (3D\u2010EVs) in a septic\u2010ALI model. Proteomic and molecular analyses of 3D\u2010EVs revealed that they are enriched in hepatocyte growth factor (HGF). HGF helps maintain the barrier function of damaged alveolar epithelium through the PI3K\u2010AKT signaling pathway. Overall, 3D\u2010EVs effectively ameliorate sepsis\u2010induced ALI and enhance prognosis by enriching and delivering HGF, suggesting that their application represents a promising treatment strategy for septic ALI.<\/jats:p>","DOI":"10.1002\/advs.202500637","type":"journal-article","created":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T21:22:12Z","timestamp":1741468932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Engineering Extracellular Vesicles Derived from 3D Cultivation of BMSCs Enriched with HGF Ameliorate Sepsis\u2010Induced Lung Epithelial Barrier Damage"],"prefix":"10.1002","volume":"12","author":[{"given":"Yong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"Shanghai Institute of Acupuncture and Anesthesia  Shanghai 200433 China"},{"name":"Department of 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