Establishment of therapeutic angiogenesis against ischemic cerebravascular disease

缺血性脑血管疾病治疗性血管生成的建立

基本信息

批准号：
15590785
负责人：
TAGUCHI Akihiko
金额：
$ 2.18万
依托单位：
National Cardiovascular Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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-15590785/
关键词：
Stroke Angiogenesis Neurogenesis Stem Cell 血管血球系細胞血管血球系幹細胞

项目摘要

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.

这项研究的目的是评估以下假设：中风后的EPCS移植可通过新血管形成来防止脑损伤。我们开发了一种与人脑缺血有关的小鼠中风模型。 MCA闭塞后48小时，将富含EPC的单核细胞静脉内移植。作为对照，我们移植EPCS贫乏的单核细胞和磷酸盐缓冲盐水。细胞移植后三个月，我们通过开放式测试和通过三苯基二甲基唑烷染色来评估小鼠行为。为了检测EPCS移植的新血管化，用供体特异性抗CD31和抗VWF抗体进行了免疫组织学检查。免疫组织学检查表明，移植的EPC被分化为内皮细胞并掺入脑新血管形成。通过EPCS移植增加脑缺血后再生脑区域。具有EPCS移植的小鼠在行为测试中表现出更好的分数。接头，我们专注于多个脑梗塞的患者。我们已经使用细胞表面标记来量化外周血中的EPC数量。结果表明，内皮细胞的周转率为3年，新形成的内皮细胞的10％是骨髓EPC的起源。与这些先前的发现一致，我们已经表明，外周血中的EPC受损与动脉硬化的进展通过减少的内皮祖细胞数量有关。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Administration of CD34+ cells post-stroke enhances neurogenesis via angiogenesis in a mouse model

中风后给予 CD34+ 细胞可通过血管生成增强小鼠模型的神经发生

DOI：
发表时间：
2004
期刊：
J.Clin.Invest. 114
影响因子：
0
作者：
Taguchi A;Soma T;Tanaka H;Kanda T;Nishimura H;Yoshikawa H;Tsukamoto Y;Iso H;Fujimori Y;Stern DM;Naritomi H;Matsuyama T
通讯作者：
Matsuyama T

Cadherin activity is required for activity-induced spine remodeling