Bone Induction by Human Bone Morphogenetic Protein Gene Transfer Using Vectors

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Bone morphogenetic protein(BMP) gene transfer using BMP-expressing vectors is the original method to force a host's own cells to make BMP ; the development of this process greatly altered the ideas of then existing BMP research. The method utilizing an adenoviral vector had good gene transfer efficiency and it was an effective technique, but the problem of immunoreaction was left to the adenovirus vector. To overcome this problem, while having the general application of an immunosuppressant and partial application, the use of a biomaterial (atelopeptide collagen) to mask the immune response etc. was examined. As the immune system could be transiently controlled by the above methods, we believed that the adenoviral vector can be applied to clinical use.Useful results were obtained in an examination of the general or partial application of an immunosuppressant on bone induction by BMP gene transfer using the BME-expressing adenoviral vector. The application of biomaterial (atelopeptide collagen) to mask the immune response succeeded in obtaining local immune suppression. Our results suggested that gene therapy with the BMP-2-expressing adenoviral vector could be performed under transient immunosuppression, with general or local application of an immunosuppressant and effective masking of the host immune response ; thus being useful for bone reconstruction.Moreover, we paid attention to a BMP-expressing plasmid vector that could be safely used in vivo, and examined gene transfer methods using the BMP-expressing plasmid vector with electroporation ; obtaining useful results. This method should soon become a very useful clinical tool for bone reconstruction, and should also contribute to the development of new treatment methods.