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.

背景从干细胞移植细胞外囊泡 (EV) 是治疗创伤性脊髓损伤 (SCI) 的可行方案。然而，目前还没有关于载有姜黄素的干细胞衍生EVs用于SCI治疗的相关报道。方法小鼠脐带间充质干细胞 (MUMSCs) 在含有姜黄素 (20 µM) 的培养基中孵育 48 小时。通过超速离心收集细胞外囊泡 (EV) 和姜黄素引发的 EV (Cur-EV)。通过使用 CD9 和 CD81 抗体的蛋白质印迹、透射电子显微镜和纳米跟踪分析来分析 EV/Cur-EV 的特征。通过高效液相色谱在 430 nm 波长下分析 Cur-EV 中的姜黄素。免疫荧光和体内成像方法用于确认 EV/Cur-EV在体外和体内的生物相容性。用 EV/Cur-EV 治疗完全 SCI 的小鼠，以比较运动功能、炎症、组织学变化和髓鞘再生的差异。结果来自 MUMSC 的分离 EV 和 Cur-EV 具有良好的生物相容性。与模型小鼠相比，注射 Cur-EVs/EVs 后小鼠的运动功能、炎症和轴突再生得到显着改善。此外，与 EVs 治疗相比，Cur-EVs 治疗后完全 SCI 的结构和功能恢复更有效。在病变区域，与 EVs 组相比，Cur-EVs 组的巨噬细胞从 M1 到 M2 表型的极化和轴突再生得到显着改善。结论我们的数据表明，来自 MUMSCs 的 EV 可能是一种很有前途的姜黄素药物递送载体，用于有效和生物相容性治疗严重 SCI。