Scalable Isolation of Human Umbilical Cord MSC-Derived Exosomes and Their Therapeutic Potential in Osteoarthritis

Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage degradation, synovial inflammation, and osteophyte formation, yet effective therapies that alter disease progression remain absent. Mesenchymal stem cell-derived exosomes (MSC-EXOs), as a cell-free regenerative medicine strategy, have shown great potential in the treatment of osteoarthritis. In this study, we successfully isolated and purified exosomes derived from human umbilical cord mesenchymal stem cells using a scalable tangential flow filtration (TFF)–chromatography platform and evaluated their therapeutic effects on OA model induced by anterior cruciate ligament transection (ACLT). OARSI scores were significantly reduced compared with the ACLT group (p < 0.01). Exosomes administration markedly reduced osteophyte formation, preserved cartilage structure, enhanced collagen II expression (p < 0.01), and suppressed MMP13-mediated matrix degradation (p < 0.05) compared with the ACLT group. The treatment also significantly decreased pro-inflammatory cytokines, indicating alleviation of the inflammatory microenvironment. Transcriptomic profiling further revealed genes and pathways potentially associated with exosome treatment. These findings suggest that hUC-MSC-EXOs isolated and purified using TFF–chromatography exert robust chondroprotective and immunomodulatory effects, supporting their potential as an effective cell-free therapeutic candidate for OA.