Extracellular vesicles released by transforming growth factor-beta 1-preconditional mesenchymal stem cells promote recovery in mice with spinal cord injury  

作　　者：Guoliang Chen Kuileung Tong Shiming Li Zerong Huang Shuangjiang Liu Haoran Zhu Yanheng Zhong Zhisen Zhou Genlong Jiao Fuxin Wei Ningning Chen 

机构地区：[1]Department of Orthopedic Surgery,The First Affiliated Hospital of Jinan University,Guangzhou,510632,China [2]Dongguan Key Laboratory of Central Nervous System Injury and Repair/Department of Orthopedic Surgery,The Sixth Affiliated Hospital of Jinan University(Dongguan Eastern Central Hospital),Dongguan,523573,China [3]Department of Orthopedic Surgery,The Seventh Affiliated Hospital,Sun Yat-sen University,Shenzhen,518107,China [4]Department of Orthopedic Surgery,The Fifth Affiliated Hospital of Jinan University(Heyuan Shenhe People’s Hospital),Heyuan,517400,China

出　　处：《Bioactive Materials》2024年第5期135-149,共15页生物活性材料（英文）

基　　金：supported by the Fundamental Research Funds for the Central Universities(No.21623310);the Dongguan Science and Technology of Social Development Program(No.20231800939902);the National Natural Science Foundation of China(No.81801907);the Guangdong Basic and Applied Basic Research Foundation(No.2022A1515140171);the Medical Joint Fund of Jinan University(No.YXJC2022011);Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research(No.ZDSYS20230626091402006).

摘　　要：Spinal cord injury(SCI)causes neuroinflammation,neuronal death,and severe axonal connections.Alleviating neuroinflammation,protecting residual cells and promoting neuronal regeneration via endogenous neural stem cells(eNSCs)represent potential strategies for SCI treatment.Extracellular vesicles(EVs)released by mesenchymal stem cells have emerged as pathological mediators and alternatives to cell-based therapies following SCI.In the present study,EVs isolated from untreated(control,C-EVs)and TGF-β1-treated(T-EVs)mesenchymal stem cells were injected into SCI mice to compare the therapeutic effects and explore the underlying mechanisms.Our study demonstrated for the first time that the application of T-EVs markedly enhanced the proliferation and antiapoptotic ability of NSCs in vitro.The infusion of T-EVs into SCI mice increased the shift from the M1 to M2 polarization of reactive microglia,alleviated neuroinflammation,and enhanced the neuroprotection of residual cells during the acute phase.Moreover,T-EVs increased the number of eNSCs around the epicenter.Consequently,T-EVs further promoted neurite outgrowth,increased axonal regrowth and remyelination,and facilitated locomotor recovery in the chronic stage.Furthermore,the use of T-EVs in Rictor/SCI mice(conditional knockout of Rictor in NSCs)showed that T-EVs failed to increase the activation of eNSCs and improve neurogenesis sufficiently,which suggested that T-EVs might induce the activation of eNSCs by targeting the mTORC2/Rictor pathway.Taken together,our findings indicate the prominent role of T-EVs in the treatment of SCI,and the therapeutic efficacy of T-EVs for SCI treatment might be optimized by enhancing the activation of eNSCs via the mTORC2/Rictor signaling pathway.

关 键 词：Endogenous neural stem cells Extracellular vesicles Mesenchymal stem cells mTORC2/rictor pathway Spinal cord injury TGF-β1 

分 类 号：R651.2[医药卫生—外科学] R329.2[医药卫生—临床医学]