2006 Fiscal Year Final Research Report Summary
Development of new method of therapeutic angiogeneis using sustained-release of multiple growth factors.
| Project/Area Number |
16390395
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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 |
Thoracic surgery
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| Research Institution | Kyoto University. |
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Principal Investigator |
IKEDA Tadashi Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (40281092)
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| Co-Investigator(Kenkyū-buntansha) |
KOMEDA Masashi Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (20303810)
TABATA Yasuhiko Kyoto University, Department of Biomaterials Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (50211371)
KITA Toru Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (60161460)
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| Project Period (FY) |
2004 – 2006
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| Keywords | therapeutic angiogenesis / growth factors / basic fibroblast growth factor / bFGF / drug delivery |
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| Research Abstract |
We have reported so far that sustained-release of basic fibroblast growth factor (bFGF) augments tissue reperfusion and functional improvement both in animal models of myocardial infarction and hindlimb ischemia. However, sustained-release of bFGF alone is not sufficient to generate stable blood vessels. Moreover, in the clinical situations, presence of diabetus or hypercholesterolemia may hamper the angiogenic effect of bFGF. To overcome these problems, we investigated the effects of adjuvant thearapies combined with sustained-release of bFGF.
In the present study, we have found that combined treatment with sustained-release bFGF and heparin synergistically enhances neovascularization in the hindlimb ischemia of hypercholesterolemic mice with impaired angiogenic responses to the ischemic stimulus. We are also reporting that 5HT receptor blocker, sarpogrerate has similar effect in diabetic rats. We also demonstrated that the sustained dual release of a lower dose of bFGF and hepatocyte growth factor (HGF) achieve equivalent tissue reperfusion and more mature vasculature in the ischemic limb than a higher dose of bFGF or HGF alone.
Using a rat model of chronic myocardial infarction, we demonstrated the sustained-release of erythropoietin improved left ventricular function without inducing polycythemia. We also examined the effect of sustained-release of granulocyte colony stimulating factor (G-CSF), which revealed no significant improvement compared with control.
From these results, we are designing clinical protocols of therapeutic angiogenesis to treat limb ischemia and choronic myocardial ischemia.
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[Journal Article] Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischemia.2007
Author(s)
Doi K, Ikeda T, Marui A, Kushibiki T, Arai Y, Hirose K, Soga Y, Iwakura A, Ueyama K, Yamahara K, Itoh H, Nishimura K, Tabata Y, Komeda M
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Journal Title
Heart and Vessels. 22(2)
Pages: 104-108
Description
「研究成果報告書概要(和文)」より
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[Journal Article] A novel approach to therapeutic angiogenesis for patients with critical limb ischemia by sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel … Initial report of the phase I-IIa study2007
Author(s)
Marui A, Tabata Y, Kojima S, Yamamoto M, Tambara K, Nishina T, Saji Y, Inui K, Hashida T, Yokoyama S, Onodera R, Ikeda T, Fukushima M, Komeda M
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Journal Title
Circulation J. (in press)
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischemia.2007
Author(s)
Doi K, Ikeda T, Marui A, Kushibiki T, Arai Y, Hirose K, Soga Y, Iwakura A, Ueyama K, Yamahara K, Itoh H, Nishimura K, Tabata Y, Komeda M.
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Journal Title
Heart and Vessels 22(2)
Pages: 104-108
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] A novel approach to therapeutic angiogenesis for patients with critical limb ischemia by sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel ---- Initial report of the phase I-IIa study.2007
Author(s)
Marui A, Tabata Y, Kojima S, Yamamoto M, Tambara K, Nishina T, Saji Y, Inui K, Hashida T, Yokoyama S, Onodera R, Ikeda T, Fukushima M, Komeda M.
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Journal Title
Circulation J. (in press)
Description
「研究成果報告書概要(欧文)」より
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