Application of newly-developed gene transfer to regeneration of bone and periodontal tissue

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As regenerative therapies for bone and periodontal tissues several methods have been developed and clinically applied ; however, a method, which is simple, safe and economical for public society, is required. Although gene transfer with plasmid DNA is safe and clinically applied, it is a problem that efficiency of this gene transfer is extremely low. In the present study, we obtained the following results.1. When plasmid DNA was combined with small Ca-phosphate particles and transplanted to the tissue defect, the efficiency of gene transfer increased. Small Ca-phosphate particles bound plasmid DNA and kept it locally. Furthermore, the binding to the particles increased the resistance to DNase. These phenomena would contribute to the increase of gene transfer.2. Utilizing this method, we applied plasmid DNA encoding human BMP2 to 5 mm segmental bone defects of rat tibias. Six weeks the defects completely healed and the mechanical strength of the bone was comparable to the normal tibia at 8 weeks. Although knot-like bone appeared at the applied site, it was gradually absorbed and the bone shape became normal.3. Similarly, plasmid DNA encoding human BMP12 was applied to the bone defects of rat femurs. Ligament-like tissue abundant in collagen fibers was formed from the previous defect to the surrounding tissue whereas the defect was filled with bone. This method would be promising for ligament reconstruction.4. Periosteum cells were cultured and these cells were transferred with BMP2 and/or VEGF gene, which were then transplanted to nude mice. When both genes were transferred, the largest amount of bone was formed.