Establishment of vascular prostheses using self endothelial precursor cell with gene modification

利用基因修饰的自体内皮前体细胞建立血管假体

• 批准号: 11557099
• 负责人: HIROSE Hajime
• 金额: $ 8.58万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557099/
• 关键词: endothelial precursor cell; gene transfer; vascular prostheses

It is an important issue to regulate the occlusion of small sized vascular prostheses, that achieve constitutive patency even in coronary artery bypass grafting (CABG). For this issue, we designed gene transferred endothelial cells coated vascular prostheses. Gene transferred self endothelial cells will prevent thrombotic occlusion or vascular stenosis associated with the endothelial proliferation and its thrombogenicity.We investigated how the endothelial cell proliferation caused the occlusion using peripheral endothelial precursor cells. Endothelial precursor cells were obtained from human peripheral blood using the anti-CD34 antibody-coated magnet beads method. We observed that CD34 positive endothelial precursor cells developed to endothelial cells in the culture with bovine brain extract, which was endothelial growth factor. Conversely, we established gene transfer system using gene gun, that achieved high gene expression.Therefore we have the next issue to apply endothelial precursor cells onto the vascular prostheses. In addition, we are going to investigate whether or not gene transfer using gene gun is useful to prevent the endothelial cell proliferation in small sized vascular prostheses.

即使在冠状动脉旁路移植术（CABG）中，调节小型人造血管的闭塞也是一个重要问题，可以实现结构性通畅。针对这一问题，我们设计了基因转移内皮细胞涂层人工血管。转基因的自体内皮细胞可以防止血栓性闭塞或血管狭窄，这与内皮细胞的增殖及其致血栓性有关，我们用外周血内皮前体细胞研究了内皮细胞增殖如何引起闭塞。使用抗CD34抗体包被磁珠法从人外周血获得内皮前体细胞。我们观察到，CD34阳性的内皮前体细胞在牛脑提取物的培养中发育为内皮细胞，这是内皮生长因子。相反，我们利用基因枪建立了基因转移系统，实现了基因的高表达，因此我们的下一个课题是将内皮前体细胞应用于人造血管。此外，我们将研究是否使用基因枪的基因转移是有用的，以防止内皮细胞增殖的小尺寸的人造血管。