Small extracellular vesicles from iPSC-derived mesenchymal stem cells ameliorate tendinopathy pain by inhibiting mast cell activation

被引:25
作者
Gao, Renzhi [1 ,2 ]
Ye, Teng [1 ,2 ]
Zhu, Zhaochen [1 ,2 ]
Li, Qing [1 ]
Zhang, Juntao [1 ]
Yuan, Ji [1 ]
Zhao, Bizeng [2 ]
Xie, Zongping [2 ]
Wang, Yang [1 ]
机构
[1] Shanghai Jiao Tong Univ, Inst Microsurg Extrem, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China
[2] Shanghai Jiao Tong Univ, Dept Orthopaed Surg, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China
基金
中国国家自然科学基金;
关键词
iMSC-sEV; mast cell; pain; tendinopathy; HYPERSENSITIVITY; DEGRANULATION; SENSITIZATION; MSC;
D O I
10.2217/nnm-2022-0036
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: This study aimed to explore the effect of small extracellular vesicles from induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-sEVs) on acute pain and investigate the underlying mechanisms. Materials & methods: The pathology of tendons was accessed by hematoxylin and eosin staining, immunohistochemical and immunofluorescent staining. The pain degree was measured by pain-related behaviors. In vitro, we performed beta-hexosaminidase release assay, RT-qPCR, toluidine blue staining, ELISA and RNA sequencing. Results: iMSC-sEVs effectively alleviated acute pain in tendinopathy as well as inhibiting activated mast cell infiltration and interactions with nerve fibers in vivo. In vitro, iMSC-sEVs reduced the degranulation of mast cells and the expression of proinflammatory cytokines and genes involved in the HIF-1 signaling pathway. Conclusion: This study demonstrated that iMSC-sEVs relieved tendinopathy-related pain through inhibiting mast cell activation via the HIF-1 signaling pathway.
引用
收藏
页码:513 / 529
页数:17
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