| Project/Area Number |
15390373
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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 |
General surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KOYAMA Hiroyuki The University of Tokyo, Faculty of Medicine, Visiting Associate Professor, 医学部附属病院, 寄附講座教員 (10241994)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Tetsuro The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (70190791)
NISHIYAMA Nobuhiro The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (10372385)
KATAOKA Kazunori The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00130245)
小見山 高士 東京大学, 医学部附属病院, 講師 (10292947)
田畑 泰彦 京都大学, 再生医科学研究所, 教授 (50211371)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | Acidic gelatin hydrogel / Polymer nano-micellsb / Reverse transfection / Intimal Hyperplasia / Rabbit carotid artery / Therapeutic angiogenesis / bFGF / RGD / 高分子ミセル型ナノパーティク / コーティング / 高分子ミセル型ナノパーティクル / RGDペプチド / Artery wall binding peptide / 治療的血管新生 / TRAF6 / 塩基性線維芽細胞増殖因子 / 血管新生療法 / 高分子ミセル型ナノ・パーティクル |
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| Research Abstract |
(1) Development of new therapeutic angiogenesis using novel bio-materials
The present study utilized acidic gelatin hydrogel microspheres (AGHM) and polymer nano-micelle particle system (NP) as novel bio-material. In AGHM, recombinant bFGF protein was bound to AGHM, and the bFGF-impregnated AGHM was administrated through targeted artery in rabbit model of chronic limb ischemia. Twenty eight days after the injection, several assessments showed significant improvement of blood perfusion and neovascularization in the ischemic limb. Meanwhile in NP, the complex with marker gene DNA was first injected to muscle tissue, and gene transfer efficiency was evaluated. However, no significant expression of marker gene was detected. To improve the efficacy of gene transfer, we added ligand peptides (RGD peptide, ring-formed RGD peptide or artery wall binding peptide) to the NP (RGD-NP, rRGD-NP and AWBP-NP). Though, these ligand-added NPs showed no significant improvement of gene transfer efficiency to muscle tissue. Therefore, we studied new gene transfer approach of NP by using reverse transfection method, and obtained favorable result under in vitro condition.
(2) Gene transfer to intimal hyperplasia using novel bio-materials
To develop gene transfer method to intimal hyperplasia of vessels, we applied NP complexed with marker gene DNA to neointimal layer of rabbit carotid artery. Although non-ligand NP, RGD-NP, rRGD-NP and AWBP-NP were examined in this study, no significant increase of gene transfer was detected as compared with control. Then, we also carried out the evaluation of new poly-ion micelle, PEG-DET, and observed favorable gene delivery to neointima of rabbit carotid artery.
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