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This study assessed the potential of programmed death\u2010ligand 1 (PD\u2010L1) and hepatocyte growth factor (HGF)\u2010engineered mesenchymal stem cell\u2010derived exosomes (EXO\u2010PD\u2010L1\u2010HGF) in enhancing neurological recovery post\u2010stroke. EXO\u2010PD\u2010L1\u2010HGF, which efficiently endocytosed into target cells, significantly diminishes the H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced neurotoxicity and increased the antiapoptotic proteins in vitro. EXO\u2010PD\u2010L1\u2010HGF attenuates inflammation by inhibiting T\u2010cell proliferation and increasing the number of CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD122\n                    <jats:sup>+<\/jats:sup>\n                    IL\u201010\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells. Intravenous injection of EXO\u2010PD\u2010L1\u2010HGF could target stromal cell\u2010derived factor\u20101\u03b1 (SDF\u20101\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    ) cells over the peri\u2010infarcted area of the ischemic brain through CXCR4 upregulation and accumulation in neuroglial cells post\u2010stroke. EXO\u2010PD\u2010L1\u2010HGF facilitates endogenous nestin\n                    <jats:sup>+<\/jats:sup>\n                    neural progenitor cell (NPC)\u2010induced neurogenesis via STAT3\u2010FOXO3 signaling cascade, which plays a pivotal role in cell survival and neuroprotection, thereby mitigating infarct size and enhancing neurological recovery in a murine stroke model. Moreover, increasing populations of the immune\u2010regulatory CD19\n                    <jats:sup>+<\/jats:sup>\n                    IL\u201010\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD122\n                    <jats:sup>+<\/jats:sup>\n                    IL\u201010\n                    <jats:sup>+<\/jats:sup>\n                    cells, together with reducing populations of proinflammatory cells, created an anti\u2010inflammatory microenvironment in the ischemic brain. Thus, innovative approaches employing EXO\u2010PD\u2010L1\u2010HGF intervention, which targets SDF\u20101\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    expression, modulates the immune system, and enhances the activation of resident nestin\n                    <jats:sup>+<\/jats:sup>\n                    NPCs, might significantly alter the brain microenvironment and create a niche conducive to inducing neuroplastic regeneration post\u2010stroke.\n                  <\/jats:p>","DOI":"10.1002\/advs.202404882","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T03:34:57Z","timestamp":1721878497000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Role of STAT3\u2010FOXO3 Signaling in the Modulation of Neuroplasticity by PD\u2010L1\u2010HGF\u2010Decorated Mesenchymal Stem Cell\u2010Derived Exosomes in a Murine Stroke Model"],"prefix":"10.1002","volume":"11","author":[{"given":"Syuan\u2010Ling","family":"Lin","sequence":"first","affiliation":[{"name":"Translational Medicine Research Center and Department of Neurology China Medical University Hospital  Taichung 404 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Wen","family":"Chang","sequence":"additional","affiliation":[{"name":"Cell Therapy Center China Medical University Hospital  Taichung 404 Taiwan"},{"name":"Department of Medical Research National Taiwan University Hospital  Taipei 100 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lee","sequence":"additional","affiliation":[{"name":"Cell Therapy Center China Medical University Hospital  Taichung 404 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Sheng","family":"Chiang","sequence":"additional","affiliation":[{"name":"Cell Therapy Center China Medical University Hospital  Taichung 404 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