Potential roles of extracellular vesicles in osteonecrosis of femoral head: A systematic review

Extracellular vesicles (EVs), have been utilised for the diagnosis and treatment of osteonecrosis of femoral head (ONFH). Hence, we aimed to review the available evidence on the potential roles of EVs in ONFH systematically. The PubMed, EMBASE, and Science Citation Index databases were searched exhaustively from inception to June 2020. All in vitro and in vivo studies on the use of EVs in ONFH diagnosis and treatment were included. The final analysis included 14 studies. These studies were categorised according to the cell source, target cell types, secreted product types, production method, storage, and study design. The animal model, together with the ONFH induction method, used in the in vivo studies was also considered. For in vivo studies, effects on cellular proliferation and apoptosis and bone and vascular tissues and biomarkers for ONFH diagnosis were assessed, whereas in the in vitro studies, effects on EVs internalization; proliferation, viability, and migration; osteogenic and adipogenic differentiation; apoptosis; and angiogenesis were evaluated. Both in vitro and in vivo studies showed promoting effects of EVs on proliferation, osteogenic differentiation, and angiogenesis and inhibitory effects on apoptosis and adipogenic differentiation in both glucocorticoid-induced and traumatic ONFH models. Additionally, EVs in blood showed diagnostic potential for ONFH. This systemic review provides a deeper understanding of the role of EVs, thereby facilitating the development of novel therapeutic strategies.