Gene therapy to improve osteogenesis in bone lesions with severe soft tissue damage.

Abstract

Ex vivo gene therapy can induce bone formation when delivery cells carrying the bone morphogenetic protein (BMP) gene are used. The hypothesis for this study was that the cell-mediated gene therapy could improve the healing of bony lesions with severe soft tissue damage. An animal model with a femoral osteotomy lesion associated with soft tissue damage was developed in rats. Muscle-derived cells, genetically engineered to express BMP4, were inserted within the osteotomy gap. Cells genetically engineered to express LacZ were used for the control group. The groups were subdivided with regard to the fixation method: stable and unstable fixation. The rats were killed for histological and radiographic evaluation 3 and 6 weeks post-surgery. No callus formation was found in the control group at any time point, whereas sufficient callus formation appeared in the treatment group after 6 weeks. A bridging callus with woven bone and hypertrophic chondrocytes was achieved in the treatment group when a stable fixation was used, but failed to appear in unstable fixation. The combination of muscle-derived cells expressing BMP4 and a stable fixation were able to bridge the bone defect within 6 weeks, but with prolonged osteochondral ossification. Therefore, the ex vivo gene therapy could be an efficient biological approach to improve the treatment of bone lesions with severe soft tissue damage.