Extracellular vesicles derived from LPS-preconditioned human synovial mesenchymal stem cells inhibit extracellular matrix degradation and prevent osteoarthritis of the knee in a mouse model

Stem Cell Research & Therapy

Beichen Li¹  Jian Qin²  Tangbo Yuan²  Wei Liu³  Feng Liu³  Cong Li³  Yuqi Shao³  Hao Zhou³  Kai Shen³  Ao Duan³  Renyi Kong⁴  Xipeng Wang⁵  Lei Li⁵  Juan Ji⁵  Tengfei Xue⁵  Wei Guo⁵  Xinxin Huang⁶  Zhenyu Cai⁶  Yuqin Sun⁶ 

[1] Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, 210001, Nanjing, Jiangsu, China;Department of Orthopedics, Sir Run Run Hospital, Nanjing Medical University, 211100, Nanjing, China;Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu, China;Department of Orthopedics, Xincheng Hospital of Traditional Chinese Medicine, 243131, Maanshan, Anhui, China;Department of Pharmacology, Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, 211100, Nanjing, China;Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu, China;

关键词: Osteoarthritis;    Extracellular vesicles;    LPS-precondition;    Let-7b;    ADAMTS5;   

DOI  :  10.1186/s13287-021-02507-2

来源: Springer

【 摘 要 】

BackgroundPrevious studies report that lipopolysaccharide (LPS)-preconditioned mesenchymal stem cells have enhanced trophic support and improved regenerative and repair properties. Extracellular vesicles secreted by synovial mesenchymal stem cells (EVs) can reduce cartilage damage caused by osteoarthritis (OA). Previous studies show that extracellular vesicles secreted by LPS-preconditioned synovial mesenchymal stem cells (LPS-pre EVs) can improve the response to treatment of osteoarthritis (OA). This study sought to explore effects of LPS-pre EVs on chondrocyte proliferation, migration, and chondrocyte apoptosis, as well as the protective effect of LPS-pre EVs on mouse articular cartilage.MethodsChondrocytes were extracted to explore the effect of LPS-pre EVs on proliferation, migration, and apoptosis of chondrocytes. In addition, the effect of LPS-pre EVs on expression level of important proteins of chondrocytes was explored suing in vitro experiments. Further, intraarticular injection of LPS-pre EVs was performed on the destabilization of the medial meniscus (DMM)-induced mouse models of OA to explore the therapeutic effect of LPS-pre EVs on osteoarthritis in vivo.ResultsAnalysis showed that LPS-pre EVs significantly promoted proliferation and migration of chondrocytes and inhibited the apoptosis of chondrocytes compared with PBS and EVs. Moreover, LPS-pre EVs inhibited decrease of aggrecan and COL2A1 and increase of ADAMTS5 caused by IL-1β through let-7b. Furthermore, LPS-pre EVs significantly prevented development of OA in DMM-induced mouse models of OA.ConclusionsLPS pretreatment is an effective and promising method to improve therapeutic effect of extracellular vesicles secreted from SMSCs on OA.

【 授权许可】

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