Integrin 101-Selected Mesenchymal Stem Cells Reduce Pain and Cartilage Degradation and Increase Immunomodulation in an Equine Osteoarthritis Model

Objective Integrin alpha 10 beta 1-selected mesenchymal stem cells (integrin alpha 10-MSCs) have previously shown potential in treating cartilage damage and osteoarthritis (OA) in vitro and in animal models in vivo. The aim of this study was to further investigate disease-modifying effects of integrin alpha 10-MSCs. Design OA was surgically induced in 17 horses. Eighteen days after surgery, horses received 2 x 107 integrin alpha 10-MSCs intra-articularly or were left untreated. Lameness and response to carpal flexion was assessed weekly along with synovial fluid (SF) analysis. On day 52 after treatment, horses were euthanized, and carpi were evaluated by computed tomography (CT), MRI, histology, and for macroscopic pathology and integrin alpha 10-MSCs were traced in the joint tissues. Results Lameness and response to carpal flexion significantly improved over time following integrin alpha 10-MSC treatment. Treated horses had milder macroscopic cartilage pathology and lower cartilage histology scores than the untreated group. Prostaglandin E2 and interleukin-10 increased in the SF after integrin alpha 10-MSC injection. Integrin alpha 10-MSCs were found in SF from treated horses up to day 17 after treatment, and in the articular cartilage and subchondral bone from 5 of 8 treated horses after euthanasia at 52 days after treatment. The integrin alpha 10-MSC injection did not cause joint flare. Conclusion This study demonstrates that intra-articular (IA) injection of integrin alpha 10-MSCs appears to be safe, alleviate pathological changes in the joint, and improve joint function in an equine post-traumatic osteoarthritis (PTOA) model. The results suggest that integrin alpha 10-MSCs hold promise as a disease-modifying osteoarthritis drug (DMOAD).