LAUSR

ABSTRACT Fractures are frequently encountered diseases troubling the senior population, and the research on fracture repair and the exploration of effective treatment methods are of great significance. This study aimed to clarify the effect of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hUMSC-EVs) on the proliferation and osteogenic differentiation of autologous bone marrow stem cells (ABMSCs). The two kinds of cells were co-cultured firstly, 5-Ethynyl-2’- deoxyuridine (EDU) staining and alizarin red staining were used to detect the proliferation and osteogenic differentiation of ABMSCs. The exosomes of hUMSCs were subsequently extracted to process ABMSCs to further test the effect on the cells. The EDU positive rate of ABMSCs and Collagen II expression were elevated, whereas the TdT-mediated dUTP nick end labeling (TUNEL) positive rate and Matrix Metallopeptidase 13 (MMP13) were markedly decreased after the co-culture of hUMSCs and ABMSCs using Transwell chamber assays. The results indicated that hUMSCs could increase the proliferation of ABMSCs, reduce apoptosis, and promote matrix metabolism. The hUMSCs exosomes were separated and added to ABMSCs. As the exosomes content increased, the proliferation of ABMSCs increased simultaneously, and ABMSCs apoptosis decreased. Meanwhile, ABMSCs that migrated to the submembrane increased compared with untreated ABMSCs. Western blot, qPCR and immunofluorescence results revealed that increased exosomes contents promoted the expression of ABMSCs anabolic-related indicators gradually, while decreased the expression of catabolism-related indicators gradually. The previously described results indicated that hUMSCs promoted the proliferation and osteogenic differentiation of ABMSCs by secreting exosomes. Graphical Abstract