Lin, Tai-ITai-ILinHsieh, Pei-YingPei-YingHsiehLin, Hui-JenHui-JenLinChiang, Cheng-KangCheng-KangChiangSheu, Jim Jinn-ChyuanJim Jinn-ChyuanSheuWEI-TIEN CHANGLiau, IanIanLiauHsu, Hsin-YunHsin-YunHsu2025-03-212025-03-212025-03-10https://scholars.lib.ntu.edu.tw/handle/123456789/726012Cerebral vascular disorders often accompany hypoxia-induced brain injury. In this study, we develop a zebrafish model of hypoxia-induced cerebral vascular injury to replicate the associated phenotypic changes, including cerebrovascular damage, neuronal apoptosis, and neurological dysfunction. We then explored the therapeutic potential of extracellular vesicles derived from Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) cultured on soy protein-coated surfaces. These vesicles demonstrated superior recovery efficacy, especially in restoring the blood-brain barrier integrity and improving neurological function. Our findings suggest that these potent therapeutic extracellular vesicles, easily produced from WJ-MSCs cultured in the presence of soy proteins, may mitigate hypoxia-induced brain injury by decreasing the severity of vascular disorder caused by oxidative stress. Protein-protein interactome analysis further suggests that multiple signaling pathways are likely involved in restoring normal neurovascular unit function.entrueextracellular vesiclesneurovascular unitsoy protein isolateszebrafish modeljournal article10.1021/acsbiomaterials.4c02304400001452-s2.0-85219055949