Overexpression of human DKK1 via rAAV vector-mediated gene transfer stimulates chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells

Enhancing the chondroregenerative activities of mesenchymal stem cells via therapeutic gene transfer as reinforced sources of implantable cells in sites of cartilage injury is a promising tool to improve the natural processes of cartilage repair. In the present study, we show that overexpression of the Dickkopf-related protein 1 (DKK1) via clinically adapted recombinant adeno-associated viral (rAAV) vectors is capable of significantly stimulating proliferative, anabolic, and chondrodifferentiation events in primary human mesenchymal stem cells compared with control (reporter rAAV lacZ) transduction over an extended period of time in vitro (21 days). Strikingly, administration of the rAAV DKK1 candidate vector concomitantly restrained unwanted osteogenic and hypertrophic differentiation outcomes in these cells. These findings reveal the possible future benefits of such an approach to treat articular cartilage lesions in relevant experimental models in vivo.