NAMPT encapsulated by extracellular vesicles from young adipose-derived mesenchymal stem cells treated tendinopathy in a "One-Stone-Two-Birds" manner.
NAMPT encapsulated by extracellular vesicles from young adipose-derived mesenchymal stem cells treated tendinopathy in a "One-Stone-Two-Birds" manner.
复制标题
DOI：
10.1186/s12951-022-01763-5
复制
发表时间：
2023-01-05
影响因子：
10.2
通讯作者：
Ge, Hengan
中科院分区：
文献类型：
--
作者：
Wu, Guanghao;Su, Qihang;Li, Jie;Xue, Chao;Zhu, Jie;Cai, Qiuchen;Huang, Jingbiao;Ji, Shaoyang;Cheng, Biao;Ge, Hengan
关键词：
肌腱病是主要的运动相关损伤，并会导致严重的无力和压痛。肌腱病的有效治疗仍然有限，脂肪组织来源的间充质干细胞（ADMSC）来源的细胞外囊泡（EV）在肌腱病治疗中表现出巨大的潜力;然而，衰老状态对EV治疗的影响尚未被描述。在这项研究中，发现与来自年轻小鼠的ADMSC（ADMSCyoung）相比，来自老年小鼠的ADMSC（ADMSCold）表现出显著的细胞衰老和受损的NAD+代谢。在ADMSCold及其分泌的EV（ADMSCCold-EV）中检测到较低的NAMPT含量。先进的动物实验表明，ADMSClod-EV，而不是ADMSClod-EV，减轻肌腱病变小鼠的病理结构，功能和生物力学特性。机制分析表明，ADMSC-EVs通过NAMPT/SIRT 1/PPARγ/PGC-1α途径提高肌腱细胞活力，缓解肌腱细胞衰老。ADMSClod-EV通过NAMPT/SIRT 1/NF-κB p65/NLRP 3途径促进巨噬细胞的吞噬作用和M2极化，而ADMSClod-EV则没有。肌腱病中的巨噬细胞/肌腱细胞串扰受到ADMSClav-EV治疗的影响，因此在肌腱病治疗中表现出“一石二鸟”效应。本研究为肌腱病提供了一种有效的新疗法，并通过阐明详细的生物学机制揭示了供体年龄对疗效的影响。在线版本包含补充材料，可通过10.1186/s12951-022-01763-5获得。
Tendinopathy 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. In 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. This study demonstrates an effective novel therapy for tendinopathy and uncovers the influence of donor age on curative effects by clarifying the detailed biological mechanism. The online version contains supplementary material available at 10.1186/s12951-022-01763-5.
登录
查看更多内容
源自低氧基于嗅觉粘膜间充质干细胞的细胞外囊泡通过miR-612增强了血管生成。
影响因子：
10.2
作者：
Ge L;Xun C;Li W;Jin S;Liu Z;Zhuo Y;Duan D;Hu Z;Chen P;Lu M
通讯作者：
Lu M
DOI：
10.1161/atvbaha.116.308187
发表时间：
2017-06-01
影响因子：
8.7
作者：
Bermudez, Beatriz;Dahl, Tuva Borresdatter;Leonardus Biessen, Erik Anna
通讯作者：
Leonardus Biessen, Erik Anna
影响因子：
37.8
作者：
Jia, Daile;Chen, Siqin;Ge, Junbo
通讯作者：
Ge, Junbo
影响因子：
82.9
作者：
Bilkei-Gorzo, Andras;Albayram, Onder;Zimmer, Andreas
通讯作者：
Zimmer, Andreas
影响因子：
12.4
作者：
Markoutsa, Eleni;Mayilsamy, Karthick;Mohapatra, Subhra
通讯作者：
Mohapatra, Subhra