Grant: Operating Grant

Bone fractures often damage the local blood vessels and soft tissues impairing the delivery of sufficient nutrients required for fracture repair. The healing of severe fractures can thus be delayed or completely stopped, leading to significant patient morbidity. Bone regeneration following a fracture requires the presence of pluripotential cells and specific growth factors. Here we propose a new technique involving bone marrow cell-based gene therapy to promote blood circulation and fracture healing. Endothelial progenitor cells (EPC) and mesenchymal stem cells (MSC) will be isolated from the bone marrow and transfected with genes encoding for vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). These modified EPC and MSC will then be delivered to a fracture site in an animal model so that they can produce VEGF and eNOS proteins. These proteins will aid in new blood vessel formation and/or osteogenesis. We hypothesize that the bone marrow cell-based gene therapy is effective in stimulating new blood vessel and bone formation. It is hoped that this work will result in a more effective strategy for improving fracture healing.