| Project/Area Number |
15590785
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
TAGUCHI Akihiko National Cardiovascular Center Research Institute, Department of Cerebravascular Disease, Group Leader, 循環動態機能部, 室長 (10359276)
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| Co-Investigator(Kenkyū-buntansha) |
NARITOMI Hiroaki National Cardiovascular Center Research Institute, Department of Cerebravascular Disease, Director, 内科脳血管部門, 部長 (60132932)
MATSUYAMA Tomohiro Hyogo Medical College, Department of Internal Medicine, Associate Prof, 医学部・総合内科, 講師 (10219529)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Stroke / Angiogenesis / Neurogenesis / Stem Cell / 血管血球系細胞 / 血管血球系幹細胞 |
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| Research Abstract |
The purpose of this study is to assess the hypothesis that EPCs transplantation after stroke prevents brain damage through neovascularization.
We developed a mouse stroke model which is relevant to human cerebral ischemia. EPC-enriched mononuclear cells are transplanted intravenously to mice 48hours after MCA occlusion. As controls, we transplant EPCs-poor mononuclear cells and phosphate-buffered salines. Three months after cell transplantation, we evaluate the mice behaviors by open field test and the regenerated brain area by Triphenyltetorazolium chloride staining. To detect the neovascularization by EPCs transplantation, immunohistological examinations were performed with donor specific anti-CD31 and anti-vWF antibody.
Our results showed that higher capillary densities around ischemic area were observed in the EPCs transplanted mice. Immunohistological examination revealed that transplanted EPCs differentiated into endothelial cells and incorporated into cerebral neovascularization. Regenerated brain area after cerebral ischemia was increased with EPCs transplantation. The mice with EPCs transplantation showed better score in behavior test.
Next, we focused on patients with multiple cerebral infarctions. We have quantified the number of EPCs in peripheral blood by fluorescence activated cell sorter using cell surface marker. It was shown that the turnover rate of endothelial cell is 3 years and 10% of newly formed endothelial cells are bone marrow EPCs origin. Consistent with these previous findings, we have shown that impaired EPCs in peripheral blood are related to the progress of arteriosclerosis through the decreased number of endothelial progenitor cells.
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