Mesenchymal stem cell–derived extracellular vesicles: A novel nanoimmunoregulatory tool in musculoskeletal diseases

The musculoskeletal system involves various cell types that participate in maintaining bone homeostasis, which is crucial for balancing osteogenesis and osteoclastogenesis. Imbalances in bone homeostasis can lead to numerous musculoskeletal disorders, including osteoarthritis (OA) and osteoporosis (OP). In recent years, there has been growing interest in osteoimmunity due to its significant regulatory impact on bone homeostasis. Various cell types, including macrophages, T cells, and B cells, participate in osteoimmunology and regulate bone homeostasis. Currently, extracellular vesicles (EVs) play crucial roles in cell-to-cell communication. In particular, mesenchymal stem cell (MSC)-derived EVs have been reported as potential immunoregulators in certain immune-related diseases. This comprehensive review aims to present recent advancements in the understanding of the immunoregulatory effects of MSC-derived EVs in musculoskeletal diseases. In addition, we discuss the immunoregulatory effects of MSC-EVs on programed cell death in osteoblasts, osteoclasts, and chondrocytes, and the effect of this modulation on bone homeostasis. Moreover, we provide insights into the potential applications of MSC-EVs in the management of prevalent musculoskeletal disorders, including OP, OA, and bone fractures. In conclusion, this review emphasizes current advancements in research and future directions in MSC-EV-based therapies for musculoskeletal disorders. • MSC-EVs are capable of treating various different types of musculoskeletal disorders. • MSC-EVs achieve the treating effects by their immuno-regulatory abilities. • Different MSC-EVs have different immunomodulatory effects, even when the sole difference lies in culture conditions. • Engineering MSC-EVs and combined with novel materials can improve the effects of MSC-EVs. • The potential for clinical applications of MSC-EVs in the field of nanomedicine is enormous.