REGIONAL GENE-THERAPY WITH A BMP-2-PRODUCING MURINE STROMAL CELL-LINEINDUCES HETEROTOPIC AND ORTHOTOPIC BONE-FORMATION IN RODENTS

The ability to continuously deliver osteoinductive proteins to a speci fic anatomic site would facilitate the treatment of fracture nonunions and other clinical problems associated with bone loss. We have develo ped a murine model of regional gene therapy. A bone-marrow stromal cel l line infected with an adenovirus expressing recombinant bone morphog enetic protein-2 cDNA secreted biologically active bone morphogenetic protein-2. These bone morphogenetic protein-2-producing cells were abl e to induce abundant heterotopic bone formation when implanted into th e quadriceps muscle of severe combined immune deficient mice and also successfully healed large segmental femoral defects in nude rats. Thes e studies demonstrate that regional gene therapy with continuous deliv ery of osteoinductive factors to a specific anatomic site can enhance the formation and repair of bone.