Bone Induction by Human Bone Morphogenetic Protein Gene Transfer Using Vectors

利用骨形态发生蛋白(BMP)表达载体进行骨形态发生蛋白(BMP)基因转移是迫使宿主自身细胞产生BMP的原始方法，这一过程的发展极大地改变了当时现有BMP研究的思路。腺病毒载体的基因转移效率高，是一种有效的方法，但免疫反应的问题留给了腺病毒载体。为了克服这一问题，在普遍应用免疫抑制剂和局部应用的同时，研究了使用生物材料(阿特洛肽胶原蛋白)来掩盖免疫反应等。由于上述方法可以暂时控制免疫系统，我们相信该腺病毒载体可以应用于临床。在使用表达BME的腺病毒载体进行BMP基因转移的骨诱导的免疫抑制剂的全身或局部应用的研究中，获得了有用的结果。应用生物材料(阿特洛肽胶原蛋白)掩盖免疫反应，成功地获得了局部免疫抑制。我们的结果表明，表达BMP-2的腺病毒载体可以在瞬时免疫抑制下进行基因治疗，全身或局部应用免疫抑制剂，并有效地掩蔽宿主的免疫反应，从而有助于骨重建。此外，我们还关注了一种可以在体内安全使用的BMP表达载体，并利用电穿孔技术对BMP表达载体的基因转移方法进行了研究，获得了有用的结果。这种方法很快就会成为骨重建的一种非常有用的临床工具，也应该有助于开发新的治疗方法。

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.