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Although the Wnt\/\u03b2-catenin signalling pathway orchestrates the development and maintenance of the BBB, the clinical translation of Wnt-based interventions remains elusive.<\/jats:p>\n                  <jats:p>We fabricated functionalized extracellular vesicles derived from neural stem cells (EVs-WK) by loading them with an engineered BBB-tropic ligand, Wnt7a-K190A, using electroporation. The therapeutic benefits of EVs-WK for BBB protection and repair were subsequently interrogated through comprehensive in vitro and in vivo analyses.<\/jats:p>\n                  <jats:p>In vitro mechanistic studies demonstrated that EVs-WK had three main effects: they enhanced BBB integrity, promoted synaptogenesis through \u03b2-catenin-mediated reinforcement and significantly attenuated neurotoxic activation of astrocytes. Cross-species validation using humanized EVs (hEVs-WK) confirmed the conserved therapeutic efficacy of this approach, as shown by the mitigation of lipopolysaccharide-induced barrier dysfunction and downregulation of inflammatory pathways. In murine intracerebral haemorrhage models, administering EVs-WK significantly reduced haematoma expansion and accelerated motor recovery.<\/jats:p>\n                  <jats:p>This modular EV platform combines BBB restoration with neurovascular unit repair, thus overcoming critical translational barriers in neurological therapeutics through targeted-controlled activation of Wnt signalling.<\/jats:p>","DOI":"10.1093\/brain\/awaf381","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T11:48:00Z","timestamp":1759837680000},"page":"447-455","source":"Crossref","is-referenced-by-count":4,"title":["Engineered neural stem cell vesicles activating Wnt promote blood\u2013brain barrier repair after cerebral haemorrhage"],"prefix":"10.1093","volume":"149","author":[{"given":"Tianwen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengshi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kezhu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chencheng","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qisheng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 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Ltd. , Shanghai 201318 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tongming","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, National Clinical Center for Geriatric Disorders, National Key Laboratory for Medical Neurobiology, Institutes of Brain Science, Shanghai Key Laboratory of Brain Function and Regeneration, Institute of Neurosurgery, MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200041 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"2026020710024401500_awaf381-B1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1161\/STROKEAHA.122.040578","article-title":"Blood-brain barrier dysfunction in normal aging and neurodegeneration: Mechanisms, impact, and treatments","volume":"54","author":"Andjelkovic","year":"2023","journal-title":"Stroke"},{"key":"2026020710024401500_awaf381-B2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10456-020-09742-w","article-title":"Vascular PDGFR-alpha protects against BBB dysfunction after stroke in 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