Targeting central nervous system extracellular vesicles enhanced triiodothyronine remyelination effect on experimental autoimmune encephalomyelitis  

作　　者：Yun Xiao Jing Tian Wen-Cheng Wu Yu-Han Gao Yu-Xin Guo Sheng-Jiao Song Rui Gao Li-Bin Wang Xiao-Yu Wu Yuan Zhang Xing Li 

机构地区：[1]National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China,The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry,The Ministry of Education,College of Life Sciences,Shaanxi Normal University,Xi’an,Shaanxi,710119,China [2]The General Hospital of Ningxia Medical University,Yinchuan,750001,China

出　　处：《Bioactive Materials》2022年第3期373-384,共12页生物活性材料（英文）

基　　金：This study was supported by the Chinese National Natural Science Foundation(Grant Nos.31970771,82071396,81771345);the Shaanxi Provincial Key R&D Foundation(Grant Nos.2021ZDLSF03-09);the Science and Technology Projects of Ningxia Autonomous Region Key R&D Programs(2018BFG02017);the Natural Science Foundation of Ningxia Province,China(Grant Nos.2020AAC03397);the Fundamental Research Funds for the Central Universities(Grant Nos.GK202007022,GK202105002,TD2020039Y,2020CSLZ009,2021CSZL008).

摘　　要：The lack of targeted and high-efficiency drug delivery to the central nervous system(CNS)nidus is the main problem in the treatment of demyelinating disease.Extracellular vesicles(EVs)possess great promise as a drug delivery vector given their advanced features.However,clinical applications are limited because of their inadequate targeting ability and the“dilution effects”after systemic administration.Neural stem cells(NSCs)supply a plentiful source of EVs on account of their extraordinary capacity for self-renewal.Here,we have developed a novel therapeutic system using EVs from modified NSCs with high expressed ligand PDGF-A(EVPs)and achieve local delivery.It has been demonstrated that EVPs greatly enhance the target capability on oligodendrocyte lineage.Moreover,EVPs are used for embedding triiodothyronine(T3),a thyroid hormone that is critical for oligodendrocyte development but has serious side effects when systemically administered.Our results demonstrated that systemic injection of EVPs+T3,versus EVPs or T3 administration individually,markedly alleviated disease development,enhanced oligodendrocyte survival,inhibited myelin damage,and promoted myelin regeneration in the lesions of experimental autoimmune encephalomyelitis mice.Taken together,our findings showed that engineered EVPs possess a remarkable CNS lesion targeting potential that offers a potent therapeutic strategy for CNS demyelinating diseases as well as neuroinflammation.

关 键 词：Extracellular vesicles NEUROINFLAMMATION Multiple sclerosis Drug delivery Experimental autoimmune encephalomyelitis T3 

分 类 号：R741[医药卫生—神经病学与精神病学]