Статья

Intranasal delivery of BDNF-loaded small extracellular vesicles for cerebral ischemia therapy

Xin‐Fu ZhouDepartment of Neurology and Stroke Center, The First Affiliated Hospital & Clinical Neuroscience Institute of Jinan University, Guangzhou 510632, PR China; Guangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou 510632, PR ChinaXiaohui DengOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR ChinaMengfan LiuGuangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou 510632, PR ChinaMeiting HeGuangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou 510632, PR ChinaWenhui LongGuangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou 510632, PR ChinaZhibin XuOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR ChinaKun ZhangDepartment of Neurology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311, Hainan, PR ChinaTao LiuDepartment of Neurology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311, Hainan, PR ChinaKwok‐Fai SoDepartment of Neurology and Stroke Center, The First Affiliated Hospital & Clinical Neuroscience Institute of Jinan University, Guangzhou 510632, PR China; Guangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou 510632, PR China; Co-innovation Center of Neuroregeneration, Nantong University, Jiangsu, PR China; Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences, Qingdao 266071, Shandong, PR China; Center for Exercise and Brain Science, School of Psychology, Shanghai University of Sport, Shanghai 200438, PR ChinaQing‐Ling FuOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China; Extracellular Vesicle Research and Clinical Translational Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: [email protected]Libing ZhouDepartment of Neurology and Stroke Center, The First Affiliated Hospital & Clinical Neuroscience Institute of Jinan University, Guangzhou 510632, PR China; Guangdong-Hongkong-Macau CNS Regeneration Institute of Jinan University, Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou 510632, PR China; Department of Neurology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311, Hainan, PR China; Co-innovation Center of Neuroregeneration, Nantong University, Jiangsu, PR China; Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences, Qingdao 266071, Shandong, PR China; Center for Exercise and Brain Science, School of Psychology, Shanghai University of Sport, Shanghai 200438, PR China. Electronic address: [email protected]

2023en

ABI

Аннотация

Mesenchymal stem cells (MSCs) have shown promise for the therapy of cerebral ischemia in animal studies and clinical trials, yet their clinical application still faces many challenges. Utilizing small extracellular vesicles (sEVs) may overcome these challenges. In the study, we overexpressed brain-derived neurotrophic factor (BDNF) in cultured MSCs and purified sEVs using anion exchange chromatography. In an ischemic stroke mouse model, sEVs selectively targeted the peri-infarct region after intranasal administration, and BDNF loading enhanced the efficacy of sEVs in improved functional behavior, neural repair indicated by infarct volume reduction, increased neurogenesis, angiogenesis, synaptic plasticity, and fiber preservation, as well as decreased inflammatory-cytokine expression and glial response. Intranasal administration of sEVs and BDNF-sEVs resulted in upregulation of neuroprotection-related genes and downregulation of inflammation-related genes, and BDNF-sEVs treatment activated the BDNF/TrkB signaling in the ischemic brain. Transcriptomic and proteomic analysis of sEVs and BDNF-sEVs disclosed abundant proteins and miRNAs involved in neuroprotection and anti-inflammation, and BDNF-sEVs showed different characteristics from sEVs. In conclusion, intranasal delivery of sEVs-loaded BDNF is a promising alternative strategy for the therapy of cerebral ischemia.

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Идентификаторы

DOI: 10.1016/j.jconrel.2023.03.033

Цитирования и источники

Цитирований: 2Использованных источников: 0

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