Integrin α10β1-Selected Mesenchymal Stem Cells Mitigate the Progression of Osteoarthritis in an Equine Talar Impact Model

Background: Early intervention with mesenchymal stem cells (MSCs) after articular trauma has the potential to limit progression of focal lesions and prevent ongoing cartilage degeneration by modulating the joint environment and/or contributing to repair. Integrin alpha 10 beta 1 is the main collagen type II binding receptor on chondrocytes, and MSCs that are selected for high expression of the alpha 10 subunit have improved chondrogenic potential. The ability of alpha 10 beta 1-selected (integrin alpha 10(high)) MSCs to protect cartilage after injury has not been investigated. Purpose: To investigate integrin alpha 10(high) MSCs to prevent posttraumatic osteoarthritis in an equine model of impact-induced talar injury. Study Design: Controlled laboratory study. Methods: Focal cartilage injuries were created on the tali of horses (2-5 years, n = 8) by using an impacting device equipped to measure impact stress. Joints were treated with 20 x 10(6) allogenic adipose-derived alpha 10(high) MSCs or saline vehicle (control) 4 days after injury. Synovial fluid was collected serially and analyzed for protein content, cell counts, markers of inflammation (prostaglandin E2, tumor necrosis factor alpha) and collagen homeostasis (procollagen II C-propeptide, collagen type II cleavage product), and glycosaminoglycan content. Second-look arthroscopy was performed at 6 weeks, and horses were euthanized at 6 months. Joints were imaged with radiographs and quantitative 3-T magnetic resonance imaging. Postmortem examinations were performed, and India ink was applied to the talar articular surface to identify areas of cartilage fibrillation. Synovial membrane and osteochondral histology was performed, and immunohistochemistry was used to assess type I and II collagen and lubricin. A mixed effect model with Tukey post hoc and linear contrasts or paired t tests were used, as appropriate. Results: Integrin alpha 10(high) MSC-treated joints had less subchondral bone sclerosis on radiographs (P = .04) and histology (P = .006) and less cartilage fibrillation (P = .04) as compared with control joints. On gross pathology, less India ink adhered to impact sites in treated joints than in controls, which may be explained by the finding of more prominent lubricin immunostaining in treated joints. Prostaglandin E2 concentration in synovial fluid and mononuclear cell synovial infiltrate were increased in treated joints, suggesting possible immunomodulation by integrin alpha 10(high) MSCs. Conclusion: Intra-articular administration of integrin alpha 10(high) MSCs is safe, and evidence suggests that the cells mitigate the effects of joint trauma.