EXTRACELLULAR VESICLES SECRETED BY OSTEOGENIC-DIFFERENTIATED MESENCHYMAL STEM CELLS PROMOTE BONE FORMATION IN RAT CALVARIAL DEFECT

Abstract

Growing evidence has suggested that paracrine mechanisms of Mesenchymal stem cell (MSC) may be involved in the underlying mechanism of MSC after transplantation, and extracellular vesicles (EVs) are an important component of this paracrine role. The aim of this study was to investigate the in vitro osteogenic effects of EVs derived from undifferentiated mesenchymal stem cells and from chemically induced to differentiate into osteogenic cells for 7 days. Further, the osteoinductive potential of EVs for bone regeneration in rat calvarial defects was assessed.We could isolate and characterize EVs from naïve and osteogenic-induced MSCs. Proteomic analysis revealed that EVs contained distinct protein profiles, with Osteo-EVs having more differentially expressed proteins with osteogenic properties. EVs were found to enhance the proliferation and migration of cultured MSC. In addition, the study found that Osteo-EVs/MEM combination scaffolds could enhance greater bone formation after 4 weeks as compared to native MEM loaded with serum-free media.The study suggests that EVs derived from chemically osteogenic-induced MSCs for 7 days can significantly enhance both the osteogenic differentiation activity of cultured hMSCs and the osteoinductivity of MEM scaffolds. The results indicate that Osteo-MSC-secreted nanocarriers-EVs combined with MEM scaffolds can be used for repairing bone defects.