Bone Induction by Human Bone Morphogenetic Protein Gene Transfer Using Vectors

使用载体通过人骨形态发生蛋白基因转移进行骨诱导

• 批准号: 15390612
• 负责人: BESSHO Kazuhisa
• 金额: $ 9.6万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390612/
• 关键词: bone morphogenetic protein; cytokine; recombinant; Escherichia Coli; plasmid; electroporation; bone induction; gene transfer

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.

骨形态发生蛋白（BMP）基因转移是利用BMP表达载体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已有的BMP研究思路。利用腺病毒载体的方法具有良好的基因转移效率，是一种有效的技术，但免疫反应的问题留给了腺病毒载体。为了克服该问题，在具有免疫抑制剂的一般应用和部分应用的同时，研究了生物材料（端肽胶原）用于掩蔽免疫应答等的用途。由于免疫系统可以通过上述方法进行瞬时控制，我们认为腺病毒载体可以应用于临床。在使用表达BME的腺病毒载体通过BMP基因转移对骨诱导的免疫抑制剂的全面或部分应用的检查中获得了有用的结果。应用生物材料（端肽胶原蛋白）来掩盖免疫反应，成功地获得了局部免疫抑制。我们的结果表明，表达BMP-2的腺病毒载体的基因治疗可以在短暂的免疫抑制下进行，全身或局部应用免疫抑制剂并有效地掩蔽宿主免疫反应;因此可用于骨重建。此外，我们关注了可以在体内安全使用的BMP表达质粒载体，并使用BMP表达质粒载体和电穿孔检查基因转移方法;获得有用的结果。这种方法应该很快成为一个非常有用的骨重建的临床工具，也应该有助于新的治疗方法的发展。

项目成果

In Vivo Study on the Effect of Nicotine on Bone Formation.

尼古丁对骨形成影响的体内研究。

• 发表时间: 2003
• 期刊: Oral Oncology 9
• 作者: Kazuhisa Bessho;Jun-ichiro Maeda;et al.
• 通讯作者: et al.

Sinji Kaihara, Kazuhisa Bessho, et al.: "Simple and Effective Osteoinductive Gene Therapy by Local Injection of a Bone Morphogenetic Protein-2-expressing Recombinant Adenoviral Vector and FK506 Mixture in Rats"Gene Therapy. 11. 439-447 (2003)

Sinji Kaihara、Kazuhisa Bessho 等人：“通过在大鼠中局部注射表达骨形态发生蛋白 2 的重组腺病毒载体和 FK506 混合物进行简单有效的骨诱导基因治疗”基因治疗。

Effect of Phosphorin on rhBMP-2-induced Bone Formation.

磷蛋白对 rhBMP-2 诱导的骨形成的影响。

• 发表时间: 2004
• 期刊: Archives of Oral Biology 49
• 作者: Takashi Saito;Fumito Kobayashi;et al.
• 通讯作者: et al.

Shinji Kaihara, Kazuhisa Bessho, et al.: "Over Expression of Bone Morphogenetic Protein-3b (BMP-3b) Using an Adenoviral Vector Promote the Osteoblastic Differentiation in C2C12 Cells and Augment the Bone Formation Induced by Bone Morphogenetic Protein-2 (

Shinji Kaihara、Kazuhisa Bessho 等人：“使用腺病毒载体过表达骨形态发生蛋白 3b (BMP-3b) 可促进 C2C12 细胞中的成骨细胞分化，并增强骨形态发生蛋白 2 诱导的骨形成（

Osteoinduction by a Human Bone Morphogenetic Protein-2 Expressing Adenoviral Vector.

表达腺病毒载体的人骨形态发生蛋白 2 的骨诱导。

• 发表时间: 2003
• 期刊: Recent Research Developments in Biophysics & Biochemistry(Research Signpost)
• 作者: Furue;M.;Kazuhisa Bessho
• 通讯作者: Kazuhisa Bessho