Human endometrial stem cells-derived exosomes enhance neurite outgrowth and peripheral nerve regeneration through activating the PI3K/AKT signaling pathway

Abstract Nowadays, exosomes participate in cell-cell communication and gain attention as a new approach for cell-free therapies. Recently, various studies have demonstrated the therapeutic ability of exosomes, but the biological effect of human endometrial stem cell (hEnSC)-derived exosomes is still unclear. Herein, we obtained exosomes from hEnSC and indicated that these exosomes activate the vital cell signaling pathway and progress neurite outgrowth in PC-12 cell lines. For this purpose, hEnSC-derived exosomes were extracted by ultracentrifuge and characterized by DLS, SEM, TEM, and western blot. Also, dil-staining of hEnSC-derived exosomes was done to determine the penetration of hEnSC-derived exosomes into PC12 cells. MTT assay, scratch assay, and western blot assay were applied to PC12 cells that were exposed to different concentrations of exosomes (0, 50, 100, and 150 µg/ml). Our results demonstrated that exosomes significantly increased neurite outgrowth, proliferation, and migration in PC12 cells in a dose-dependent manner. Moreover, the analysis of western blots showed increased expression of the PI3/AKT signaling pathway in PC12 cells exposed to hEnSC-derived exosomes in a dose-dependent manner. Also, the results of this study indicated that hEnSC-derived exosomes can enhance cell proliferation and migration and promote neural outgrowth by activating the PI3/AKT signaling pathway. Accordingly, hEnSC-derived exosomes became an effective strategy for cell-free therapies. All together, these positive effects make hEnSC-derived exosomes a new efficient approach in regenerative medicine, especially for the cure of neural injury.