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 α10β1-selected MSCs (integrin α10-MSCs), to a cartilage defect in a rabbit model and 2) the ability of the integrin a10-MSCs to differentiate to chondrocytes and to produce cartilage matrix molecules in vivo .

Design:

Integrin α10-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 α10-MSCs or vehicle were injected into the joint. Migration and distribution of the SPION-labeled integrin α10-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 α10-MSCs demonstrated maintained viability, proliferation rate and tri-lineage differentiation capacity compared to unlabeled MSCs. In vivo MRI analysis detected the labeled integrin α10-MSCs in the cartilage defects at all time points from 12 hours after injection until day 10 with a peak concentration between day 1-4 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 α10-MSCs in all layers of the cartilage repair tissue and showed co-localization between the MSCs 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 α10-MSC treatment were detected during the study period.

Conclusion:

Our results demonstrated migration and homing of human integrin α10β1-selected MSCs to cartilage defects in the rabbit knee after intra-articular administration indicating that the MSCs have a direct role in the cartilage regeneration.