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

Supplementary Information Abstract Aims: This study aimed to explore the effect of iMSC-sEVs on acute pain and investigate the underlying mechanisms. Materials & Methods: The pathology of tendon was accessed by H&E staining, immunohistochemical and immunofluorescent staining. The pain degree was measured by pain-related behaviors. In vitro, we performed -Hexosaminidase release assay, RT-qPCR, Toluidine blue staining, ELISA and RNA-seq. Results: iMSC-sEVs effectively alleviated acute pain in tendinopathy as well as inhibited activated mast cell infiltration and interactions with nerve fibers in vivo. In vitro, iMSC-sEVs reduced the degranulation of mast cells, the expression of proinflammatory cytokines and genes involved in the HIF-1 signaling pathway. Conclusions: This study demonstrated iMSC-sEVs relieved tendinopathy-related pain through inhibiting mast cells activation via the HIF-1 signaling pathway.