{"title":"来自脐带间充质干细胞的外泌体通过miR-664a-5p调节AAK1改善小鼠缺血性脑损伤。","authors":"Baoxi Shen, Ning Liu, Yiwu Dai","doi":"10.1080/00207454.2024.2441120","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To identify the molecular targets of mesenchymal stem cell (MSC)-derived exosomes in treating cerebral ischemia and elucidate their therapeutic mechanisms.</p><p><strong>Methods: </strong>We utilized a mouse model of middle cerebral artery occlusion and treated mice with umbilical cord mesenchymal stem cells derived exosomes. Proteomic analysis identified AAK1(AP2 associated kinase 1) as a key target protein. Functional studies confirmed that AAK1 modulates the NF-κB signaling pathway in ischemic stroke. MicroRNA profiling, bioinformatic prediction and cell experiments identified miR-664a-5p as the specific microRNA regulating AAK1 expression. Finally, we validated the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes using engineered miR-664a-5p-deficient exosomes.</p><p><strong>Results: </strong>Our findings demonstrate that umbilical cord mesenchymal stem cells-derived exosomes exert neuroprotective effects in ischemic stroke by modulating the AAK1/NF-κB axis <i>via</i> miR-664a-5p.</p><p><strong>Conclusion: </strong>This study provides novel insights into the therapeutic mechanism of mesenchymal stem cell-derived exosomes in ischemic stroke, highlighting their potential for developing exosome-based therapies.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1-15"},"PeriodicalIF":1.7000,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exosomes derived from umbilical cord mesenchymal stem cells ameliorate ischemic brain injury in mice by regulating AAK1 via miR-664a-5p.\",\"authors\":\"Baoxi Shen, Ning Liu, Yiwu Dai\",\"doi\":\"10.1080/00207454.2024.2441120\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To identify the molecular targets of mesenchymal stem cell (MSC)-derived exosomes in treating cerebral ischemia and elucidate their therapeutic mechanisms.</p><p><strong>Methods: </strong>We utilized a mouse model of middle cerebral artery occlusion and treated mice with umbilical cord mesenchymal stem cells derived exosomes. Proteomic analysis identified AAK1(AP2 associated kinase 1) as a key target protein. Functional studies confirmed that AAK1 modulates the NF-κB signaling pathway in ischemic stroke. MicroRNA profiling, bioinformatic prediction and cell experiments identified miR-664a-5p as the specific microRNA regulating AAK1 expression. Finally, we validated the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes using engineered miR-664a-5p-deficient exosomes.</p><p><strong>Results: </strong>Our findings demonstrate that umbilical cord mesenchymal stem cells-derived exosomes exert neuroprotective effects in ischemic stroke by modulating the AAK1/NF-κB axis <i>via</i> miR-664a-5p.</p><p><strong>Conclusion: </strong>This study provides novel insights into the therapeutic mechanism of mesenchymal stem cell-derived exosomes in ischemic stroke, highlighting their potential for developing exosome-based therapies.</p>\",\"PeriodicalId\":14161,\"journal\":{\"name\":\"International Journal of Neuroscience\",\"volume\":\" \",\"pages\":\"1-15\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-12-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/00207454.2024.2441120\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00207454.2024.2441120","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Exosomes derived from umbilical cord mesenchymal stem cells ameliorate ischemic brain injury in mice by regulating AAK1 via miR-664a-5p.
Objective: To identify the molecular targets of mesenchymal stem cell (MSC)-derived exosomes in treating cerebral ischemia and elucidate their therapeutic mechanisms.
Methods: We utilized a mouse model of middle cerebral artery occlusion and treated mice with umbilical cord mesenchymal stem cells derived exosomes. Proteomic analysis identified AAK1(AP2 associated kinase 1) as a key target protein. Functional studies confirmed that AAK1 modulates the NF-κB signaling pathway in ischemic stroke. MicroRNA profiling, bioinformatic prediction and cell experiments identified miR-664a-5p as the specific microRNA regulating AAK1 expression. Finally, we validated the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes using engineered miR-664a-5p-deficient exosomes.
Results: Our findings demonstrate that umbilical cord mesenchymal stem cells-derived exosomes exert neuroprotective effects in ischemic stroke by modulating the AAK1/NF-κB axis via miR-664a-5p.
Conclusion: This study provides novel insights into the therapeutic mechanism of mesenchymal stem cell-derived exosomes in ischemic stroke, highlighting their potential for developing exosome-based therapies.
期刊介绍：
The International Journal of Neuroscience publishes original research articles, reviews, brief scientific reports, case studies, letters to the editor and book reviews concerned with problems of the nervous system and related clinical studies, epidemiology, neuropathology, medical and surgical treatment options and outcomes, neuropsychology and other topics related to the research and care of persons with neurologic disorders. The focus of the journal is clinical and transitional research. Topics covered include but are not limited to: ALS, ataxia, autism, brain tumors, child neurology, demyelinating diseases, epilepsy, genetics, headache, lysosomal storage disease, mitochondrial dysfunction, movement disorders, multiple sclerosis, myopathy, neurodegenerative diseases, neuromuscular disorders, neuropharmacology, neuropsychiatry, neuropsychology, pain, sleep disorders, stroke, and other areas related to the neurosciences.
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