Bone Formation by BMP Gene Transfection

An application of bone morphogenetic proteins (BMPs) has been expected to be a solution for fracture repair and bone regeneration ever since the discovery of their osteogenic potential (Urist, 1965; Reddi, 2000). Recombinant BMPs have been employed in in vitro and in vivo studies of bone induction. In vitro studies have revealed that BMPs cause the transformation of pluripotent mesenchymal cells obtained from bone marrow (Thies et al., 1992), fat (Dragoo et al., 2003), and muscle (Katagiri et al., 1994) into osteogenic cells. Clinical application of recom-binant BMPs requires a high-quality recombinant protein and drug delivery system (DDS), which enables slow and continuous release of protein.

Vectors for gene transfer can be categorized into two groups: viral and nonviral. In vivo transfer of BMP gene by adenoviral vector could induce ectopic bone in muscle (Musgrave et al., 1999; Gonda et al., 2000; Chen et al., 2002). However, adenoviral vector causes an immune response. Obvious ectopic bone formation was detected in immunodeficient animals, but less so in immunocompetent animals (Musgrave et al., 1999; Li et al., 2003). Transplantation of adenoviral infected cells is more promis ing, and bone formation could be achieved in immunocompetent animals (Chang et al., 2003; Wang et al., 2003). Systemic administration (Okubo et al., 2000) and local administration (Kaihara et al., 2004) of immunosuppressant can decrease the immune response of the host and enables adenoviral infection and effective bone formation. The use of retroviral vector also is possible to transfect BMP gene and induce bone formation. Adenoassociated viral transfer (AAV) (Gafni et al., 2004) and helper-dependent adenoviral transfer (Abe et al., 2002) are less pathogenic and can be candidates for gene therapy of immunocompetent animals.