Genetically engineered periodontal cells as a potential source in bone-regeneration

Objectives: The success of ex-vivo gene therapy relies on their large-scale purification and production of signaling molecules as well as methods to deliver these factors to their targets. The genetically altered cells have typically been fibroblasts or myoblasts that are easily biopsied and propagated in vitro. BMPs play pivotal roles in bone tissue repair, induce ectopic bone formation and enhance repair of fracture. The use of BMP-2 transduced fibroblasts can contribute to bone formation and induce host tissues to produce bone. Here we report that BMP-2 transduced gingival fibroblasts were responsive to BMP-2 similarly with periodontal ligament cells and osteoblast cells and could induce an osteoblastic conversion of nonosteoblastic fibroblasts. Methods: To examine abilities of fibroblasts in periodontium as gene delivery carrier, osteogenesis of the cells by BMP-2 gene and responsive to BMP-2, we investigated cell proliferation, mineralization and cell signaling by BMP-2. Results: The numbers of cells were increased in accordance with culture periods, respectively and ad5 virus didn't show toxic effect on the cells. All the cells infected with ad5BMP2 showed increased ALPase activity and mineralization. Phosphorylation of smad1/5/8 protein was enhanced by ad5BMP2 and rhBMP2. Conclusion: This study demonstrated the PDL and GF cell can be alter the phenotype from fibroblastic to osteoblastic. For ex vivo gene therapy, use of cells such PDL and GF cells may improve the healing in bone defect by the bone production of donor cells as well as supplying of BMP2. Further studies using animal model needs to confirm production of bone in vivo and searching the safer vector needs for avoiding adverse effect of virus vector. This study was supported by the grant from Ministry of Commerce, Industry and Energy: Development of Medical Devices for the Old Age (2004-00633)