Integrin α10β1-selected equine mesenchymal stem cells reduce lameness and joint degradation and increase immunomodulatory factors interleukin-10 and prostaglandin E2 in experimental post-traumatic osteoarthritis

Abstract

Abstract Background Mesenchymal stem cells (MSCs) have gained much attention for their potential to treat osteoarthritis (OA). Integrin α10β1-selected equine MSCs (integrin α10-MSCs) have previously been shown to decrease cartilage degradation and bone sclerosis in an experimental equine post-traumatic osteoarthritis (OA) model, and recently we demonstrated that human integrin α10β1-selected MSCs were able to home to experimental cartilage defects in rabbit knees and directly participate in cartilage regeneration. The aim of this study was to further investigate disease modifying effects of integrin α10β1-selected MSCs with respect to joint function, cartilage health and immunomodulation in an experimental equine post-traumatic OA-model. Design In this non-randomized, partially blinded experimental case-control study, OA was induced using a carpal osteochondral fragment model in female horses. Eighteen days after surgery, eight horses received 2 x 107 male integrin α10-MSCs intra-articularly and 9 were left untreated. Lameness, response to carpal flexion, carpal skin temperature and circumference was assessed weekly, along with synovial fluid analysis of inflammatory mediators. After euthanasia (70 days after OA induction), carpi were evaluated by computed tomography (CT) and magnetic resonance imaging (MRI), macroscopic pathology, and histology. The integrin α10-MSCs were traced by Y-chromosome PCR. Results Lameness, response to carpal flexion and carpal skin temperature were significantly improved over time after integrin α10-MSC treatment. The treated horses had significantly milder macroscopic cartilage pathology and lower cartilage histology scores compared to the untreated group. Prostaglandin E2 and interleukin-10 increased in the synovial fluid after integrin α10-MSC injection. MSCs were found in the synovial fluid of treated horses up to day 17 after treatment and in the articular cartilage and subchondral bone in five out of eight treated horses after euthanasia, 52 days after integrin α10-MSC treatment. The integrin α10-MSC injection did not cause any signs of joint flare. Conclusion This study demonstrates that intra-articular injection of integrin α10-MSCs is safe, alleviate pathological changes in the joint and improve joint function in an equine OA model. The results suggest that integrin α10-MSCs hold potential to be a disease modifying treatment of OA.