Human integrin α10β1-selected mesenchymal stem cells home to cartilage defects in the rabbit knee and assume a chondrocyte-like phenotype

Background: Mesenchymal stem cells (MSCs) have shown promising results in stimulating cartilage repair and in the treatment of osteoarthritis (OA). However, the fate of the MSCs after intra-articular injection and their role in cartilage regeneration is not clear. To address these questions, this study investigated (1) homing of labeled human adipose tissue derived integrin alpha 10 beta 1-selected MSCs (integrin alpha 10-MSCs) to a cartilage defect in a rabbit model and (2) the ability of the integrin alpha 10-MSCs to differentiate to chondrocytes and to produce cartilage matrix molecules in vivo. Design: Integrin alpha 10-MSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) co-conjugated with Rhodamine B to allow visualization by both MRI and fluorescence microscopy. A cartilage defect was created in the articular cartilage of the intertrochlear groove of the femur of rabbits. Seven days post-surgery, labeled integrin alpha 10-MSCs or vehicle were injected into the joint. Migration and distribution of the SPION-labeled integrin alpha 10-MSCs was evaluated by high-field 9.4T MRI up to 10 days after injection. Tissue sections from the repair tissue in the defects were examined by fluorescence microscopy. Results: In vitro characterization of the labeled integrin alpha 10-MSCs demonstrated maintained viability, proliferation rate and trilineage differentiation capacity compared to unlabeled MSCs. In vivo MRI analysis detected the labeled integrin alpha 10-MSCs in the cartilage defects at all time points from 12 h after injection until day 10 with a peak concentration between day 1 and 4 after injection. The labeled MSCs were also detected lining the synovial membrane at the early time points. Fluorescence analysis confirmed the presence of the labeled integrin alpha 10-MSCs in all layers of the cartilage repair tissue and showed co-localization between the labeled cells and the specific cartilage molecules aggrecan and collagen type II indicating in vivo differentiation of the MSCs to chondrocyte-like cells. No adverse effects of the alpha 10-MSC treatment were detected during the study period. Conclusion: Our results demonstrated migration and homing of human integrin alpha 10 beta 1-selected MSCs to cartilage defects in the rabbit knee after intra-articular administration as well as chondrogenic differentiation of the MSCs in the regenerated cartilage tissue.