Curcumin-Primed Umbilical Cord Mesenchymal Stem Cells-Derived Extracellular Vesicles Improve Motor Functional Recovery of Mice with Complete Spinal Cord Injury by Reducing Inflammation and Enhancing Axonal Regeneration

Background Transplantation of extracellular vesicles (EVs) from stem cells is a feasible scheme for traumatic spinal cord injury (SCI). However, there is no relevant report about stem cells derived EVs loaded with curcumin for SCI treatment. Methods Mouse umbilical cord mesenchymal stem cells (MUMSCs) were incubated in the medium containing curcumin (20 µM) for 48 h. Extracellular vesicles (EVs) and curcumin-primed EVs (Cur-EVs) were collected by ultracentrifugation. Characterizations of EVs/Cur-EVs were analyzed by western blotting with CD9 and CD81 antibodies, transmission electron microscopy and nano-tracking analysis. Curcumin in the Cur-EVs was analyzed by high performance liquid phase chromatography at 430 nm wavelength. Immunofluorescence and in vivo imaging methods were used to confirm biocompatibility of EVs/Cur-EVs in vitro and in vivo . Mice with complete SCI were treated with EVs/Cur-EVs to compare the differences of locomotor function, inflammation, histological changes and remyelination. Results The isolated EVs and Cur-EVs from MUMSCs have good biocompatibility. Compared with the model mice, the locomotor function, inflammation and axonal regeneration of mice were significantly improved after injection of Cur-EVs/EVs. Furthermore, it is more effective for structural and functional recovery of complete SCI after the Cur-EVs treatment compared with the EVs treatment. In the lesioned regions, the macrophage polarization from M1 to M2 phenotype and axonal regeneration were significantly improved in the Cur-EVs group compared with the EVs group. Conclusions Our data suggested that EVs from MUMSCs might be a promising drug delivery vehicle of curcumin for the efficient and biocompatible treatment of severe SCI.