| Project/Area Number |
16390579
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KASUGAI Shohei Tokyo Medical and Dental University, Graduate School, Prof, 大学院医歯学総合研究科, 教授 (70161049)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Hisatomo Tokyo Medical and Dental University, Graduate School, Research Associate, 大学院医歯学総合研究科, 助手 (70343150)
KURODA Shinji Tokyo Medical and Dental University, Dental Hospital, Research Associate, 歯学部附属病院, 助手 (50323689)
ASAHINA Izumi Nagasaki University, Graduate School, Prof, 医歯薬学総合研究科, 教授 (30221039)
ODA Shigeru Tokyo Medical and Dental University, Graduate School, Lecturer, 大学院医歯学総合研究科, 講師 (70160869)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | Gene Transfer / Plasmid DNA / BMP / Bone / Periodontal tissue / Tissue Regeneration / Collagen / Ligament / プラスミドDNA / 再生医療 |
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| Research Abstract |
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.
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