NAMPT encapsulated by extracellular vesicles from young adipose-derived mesenchymal stem cells treated tendinopathy in a “One-Stone-Two-Birds” manner

Journal of Nanobiotechnology

Research

Qihang Su¹  Jingbiao Huang¹  Qiuchen Cai¹  Chao Xue¹  Hengan Ge²  Biao Cheng²  Jie Li³  Jie Zhu⁴  Shaoyang Ji⁴  Guanghao Wu⁵ 

[1] Department of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, 200072, Shanghai, China;Department of Orthopedics, Tongji Hospital, School of Medicine, Tongji University, 200065, Shanghai, China;Department of Orthopedics, Zhabei Central Hospital of Jing’an District, 200070, Shanghai, China;National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 100190, Beijing, China;School of Materials Science and Engineering, Beijing Institute of Technology, 100081, Beijing, China;

关键词: Extracellular vesicles;    Adipose tissue-derived mesenchymal stem cells;    NAD+ metabolism;    Macrophage;    Tendinopathy;   

DOI  :  10.1186/s12951-022-01763-5

 received in 2022-10-05, accepted in 2022-12-27,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundTendinopathy is the leading sports-related injury and will cause severe weakness and tenderness. Effective therapy for tendinopathy remains limited, and extracellular vesicles (EVs) derived from adipose tissue-derived mesenchymal stem cells (ADMSCs) have demonstrated great potential in tendinopathy treatment; however, the influence of aging status on EV treatment has not been previously described.ResultsIn this study, it was found that ADMSCs derived from old mice (ADMSCold) demonstrated remarkable cellular senescence and impaired NAD+ metabolism compared with ADMSCs derived from young mice (ADMSCyoung). Lower NAMPT contents were detected in both ADMSCold and its secreted EVs (ADMSCold-EVs). Advanced animal experiments demonstrated that ADMSCyoung-EVs, but not ADMSCold-EVs, alleviated the pathological structural, functional and biomechanical properties in tendinopathy mice. Mechanistic analyses demonstrated that ADMSCyoung-EVs improved cell viability and relieved cellular senescence of tenocytes through the NAMPT/SIRT1/PPARγ/PGC-1α pathway. ADMSCyoung-EVs, but not ADMSCold-EVs, promoted phagocytosis and M2 polarization in macrophages through the NAMPT/SIRT1/Nf-κb p65/NLRP3 pathway. The macrophage/tenocyte crosstalk in tendinopathy was influenced by ADMSCyoung-EV treatment and thus it demonstrated "One-Stone-Two-Birds" effects in tendinopathy treatment.ConclusionsThis study demonstrates an effective novel therapy for tendinopathy and uncovers the influence of donor age on curative effects by clarifying the detailed biological mechanism.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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