Small Extracellular Vesicles From iPSC-Derived Mesenchymal Stem Cells Ameliorate Tendinopathy Pain by Inhibiting Mast Cell Activation

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 β-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.