Project 176425

Bone fracture disrupts the circulation around a fracture and leads to acute necrosis and hypoxia of adjacent bone and marrow. Severe fracture may lead to delays in bone healing or nonunion. There are only a limited number of effective treatment options to enhance fracture healing. The present research proposal seeks to develop a novel approach, namely bone marrow cell-based gene therapy to promote fracture healing using bone marrow derived endothelial progenitor cell (EPC) and mesenchymal stem cell (MSC) transfer with genes of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). It is hypothesized that bone marrow cell-based gene transfer without virus vector therapy applied to a fracture, may be effective in stimulating angiogenesis and enhancing new bone formation locally. The transfected cells will be delivered to the animal fracture site. The EPCs and MSCs then function as a factory to produce VEGF and eNOS proteins and the other phenotypic characteristics of the EPCs or MSCs which favor neovascularization or differentiation into osteoblasts are retained. It is hoped that this work will lead to novel and more effective strategies to increase fracture healing and to reduce non-union following fracture.