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Potential usage of endothelial progenitor cells (EPC) in neovascularization

内皮祖细胞 (EPC) 在新生血管形成中的潜在用途

基本信息

批准号：
15500313
负责人：
YOSHIDA Masayuki
金额：
$ 2.05万
依托单位：
Tokyo Medical and Dental University
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-15500313/
关键词：
progenitor cells adhesion molecule neovascularization 血管内費前駆細胞

项目摘要

In this project, we investigated potential usage of endothelial progenitor cells (EPC) in neovascularization especially molecular mechanisms that support their adhesion to mature vascular endothelium. In the first year of the project, we were able to establish culture system of EPC in vitro. Moreover, we conducted an adhesion assay under physiological flow condition using EPC. We found that cytokine activation of vascular endothelium significantly upregulated adhesion of EPC when compared to unactivated endothelium. When we pretreated these vascular endothelium with adhesion blocking antibodies against E-selectin, ICAM 1, and VCAM-1, anti-E-selectin antibody but not other antibodies blocked adhesion of EPC to endothelium, suggesting an important role for E-selectin in EPC adhesion. In the second year, we developed a neovascularization model using ischemic hindlimb in nude mice. Injection of EPC to these mice significantly improved their neovascularization in the hindlimb as previously reported. When amount of EPC was reduced to one-fifth of the optimal number, the recovery of blood flow was significantly attenuated. However, when adenovirus containing E-selectin cDNA was introduced to express E-selectin, neovascularization was significantly restored. These data suggested that potential efficacy of E-selectin in neovascularization.

在这个项目中，我们研究了内皮祖细胞（EPC）在新生血管中的潜在用途，特别是支持其粘附到成熟血管内皮的分子机制。在项目的第一年，我们能够在体外建立EPC培养体系。此外，我们还使用EPC进行了生理流动条件下的粘附实验。我们发现，与未激活的内皮相比，激活血管内皮的细胞因子显著上调EPC的粘附。当我们用抗e -选择素、ICAM 1和VCAM-1的粘附阻断抗体预处理这些血管内皮时，抗e -选择素抗体而非其他抗体阻断了EPC与内皮的粘附，提示e -选择素在EPC粘附中起重要作用。第二年，我们建立了裸鼠后肢缺血新生血管模型。如前所述，向这些小鼠注射EPC可显著改善其后肢新生血管的形成。当EPC数量减少到最佳数量的五分之一时，血流恢复明显减弱。然而，当引入含有e -选择素cDNA的腺病毒表达e -选择素时，新生血管明显恢复。这些数据提示e -选择素在新生血管中的潜在功效。