Abstract
Recently, exosomes have been extensively applied in tissue regeneration. However, their practical applications are severely restricted by the limited exosome secretion capability of cells. Therefore, developing strategies to enhance the production of exosomes and improve their biological function attracts great interest. Studies have shown that biomaterials can significantly enhance the paracrine effects of cells and exosomes are the main signal carriers of intercellular paracrine communication, thus biomaterials are considered to affect the exosome secretion of cells and their biological function. In this study, a widely recognized biomaterial, 45S5 Bioglass® (BG), is used to create a mild and cell-friendly microenvironment for mesenchymal stem cells (MSCs) with its ion products. Results showed that BG ion products can significantly improve exosome production of MSCs by upregulating the expression of neutral sphingomyelinase-2 (nSMase2) and Rab27a which enhanced the nSMases and Rab GTPases pathways, respectively. Besides, microRNA analysis indicates that BG ion products can modulate the cargoes of MSCs-derived exosomes by decreasing microRNA-342-5p level while increasing microRNA-1290 level. Subsequently, the function of exosomes is modified as their capabilities of promoting the vascularization of endothelial cells and facilitating the intradermal angiogenesis are enhanced. Taken together, BG ion products are confirmed to enhance exosome production and simultaneously improve exosome function, suggesting a feasible approach to improve the practical application of exosomes in regenerative medicine.