Mechanisms and Therapeutic Potential of Stem Cell‐Derived Extracellular Vesicles as Nanocarriers in Musculoskeletal Disorders

The musculoskeletal system consists of bones, joint cartilage, tendons, ligaments, muscles, and their associated nerves and blood vessels. These components work together to maintain human movement and mechanical stability, serving as the critical foundation for sustaining life activities. In recent years, with the acceleration of population aging, the incidence of musculoskeletal-related diseases such as sarcopenia, muscle atrophy, osteoporosis (OP), osteoarthritis (OA), and tendon injuries has continued to rise, significantly impacting patients' quality of life and imposing a heavy social health burden. Mesenchymal stem cells (MSCs) have garnered widespread attention in tissue repair and regenerative medicine due to their excellent self-renewal capacity, multipotent differentiation potential, and low immunogenicity. Numerous studies have shown that the therapeutic effects of MSCs primarily depend on their paracrine actions, particularly the extracellular vesicles (EVs) they secrete, which play a crucial role in regulating tissue homeostasis and repairing damage. MSC-derived EVs possess biological functions similar to those of their parent cells and lack immunogenicity and tumorigenic risks. As effective carriers of intercellular signaling, they can transport various bioactive substances (such as miRNAs, mRNAs, proteins, and lipids), demonstrating significant advantages in regulating cellular functions within the musculoskeletal system, promoting tissue regeneration, and alleviating inflammation. This paper provides a systematic review of the research progress of MSC-derived EVs in musculoskeletal system diseases, focusing on their mechanisms of action and application potential in sarcopenia, osteoporosis, degenerative joint cartilage diseases, and tendon repair, aiming to provide theoretical basis and new research directions for related basic research and clinical translation.