Gao Renzhi, Ye Teng, Zhu Zhaochen, Li Qing, Zhang Juntao, Yuan Ji, Zhao Bizeng, Xie Zongping, Wang Yang
Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
Nanomedicine (Lond). 2022 Apr;17(8):513-529. doi: 10.2217/nnm-2022-0036. Epub 2022 Mar 15.
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. The pathology of tendons was accessed by hematoxylin and eosin staining, immunohistochemical and immunofluorescent staining. The pain degree was measured by pain-related behaviors. , we performed β-hexosaminidase release assay, RT-qPCR, toluidine blue staining, ELISA and RNA sequencing. iMSC-sEVs effectively alleviated acute pain in tendinopathy as well as inhibiting activated mast cell infiltration and interactions with nerve fibers . , iMSC-sEVs reduced the degranulation of mast cells and the expression of proinflammatory cytokines and genes involved in the HIF-1 signaling pathway. This study demonstrated that iMSC-sEVs relieved tendinopathy-related pain through inhibiting mast cell activation via the HIF-1 signaling pathway.
本研究旨在探讨诱导多能干细胞来源的间充质干细胞小细胞外囊泡（iMSC-sEVs）对急性疼痛的影响，并研究其潜在机制。通过苏木精和伊红染色、免疫组织化学和免疫荧光染色来评估肌腱的病理情况。通过与疼痛相关的行为来测量疼痛程度。我们进行了β-己糖胺酶释放试验、RT-qPCR、甲苯胺蓝染色、酶联免疫吸附测定（ELISA）和RNA测序。iMSC-sEVs有效减轻了肌腱病中的急性疼痛，并抑制了活化肥大细胞的浸润以及与神经纤维的相互作用。此外，iMSC-sEVs减少了肥大细胞的脱颗粒以及促炎细胞因子和参与缺氧诱导因子-1（HIF-1）信号通路的基因的表达。本研究表明，iMSC-sEVs通过HIF-1信号通路抑制肥大细胞活化，从而缓解肌腱病相关疼痛。
