Human Umbilical Cord Mesenchymal Stem Cell‐Derived Exosomes Preserve Cartilage Homeostasis and Restore Joint Function in Experimental Osteoarthritis

Mesenchymal stem cells (MSCs) have shown therapeutic potential for osteoarthritis (OA), but their clinical application is limited by the need for extensive ex vivo expansion. Human umbilical cord MSC-derived exosomes (hUCMSC-Exos) have emerged as a promising cell-free alternative because of their cartilage-protective and immunomodulatory properties. hUCMSC-Exos were characterized by nanoparticle tracking analysis and evaluated in an interleukin-1β (IL-1β)-stimulated human chondrocyte model and an anterior cruciate ligament transection (ACLT)-induced rat OA model. In vitro, hUCMSC-Exos suppressed inflammatory and catabolic responses while enhancing extracellular matrix synthesis, as evidenced by reduced IL-1β, MMP13, and Type X collagen expression and increased TIMP1, aggrecan, and Type II collagen expression. In vivo, repeated intra-articular administration of hUCMSC-Exos attenuated cartilage degeneration, resulting in improved gross joint morphology, reduced histopathological damage, increased glycosaminoglycan deposition and Type II collagen expression, and decreased MMP13 expression. These structural improvements were accompanied by enhanced functional recovery, as demonstrated by improved hind limb weight-bearing and treadmill running endurance. These findings suggest that hUCMSC-Exos alleviate cartilage degeneration and improve joint function, supporting their potential as a promising cell-free therapeutic approach for OA.