Novel angiogenic gene therapy for the treatment of ischemic limb

治疗肢体缺血的新型血管生成基因疗法

基本信息

批准号：
13557098
负责人：
MIYATA Tetsuro
金额：
$ 6.53万
依托单位：
THE UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557098/
关键词：
Angiogenic therapy bFGF VEGF Ephrin B2 Rabbit Gene therapy Ex vivo Eph B4 CD40リガンドウサギポリエチレンイミン Therapeutic angiogenesis Ephrine B2 血管新生ラテンウイエルス Ex vivo ラビット虚血肢

项目摘要

Previously, we developed novel angiogenic therapy for the treatment of ischemic limbs, in which auto-fibroblasts, adenoviraIly transduced with modified bFGF gene, were infused into the ischemic limb thorugh an intra-arterial catheter (ex vivo method). In the present study, we determined (1)how many gene-transduced fibroblasts induced appropriate therapeutic effects and (2)which angiogenic growth factor effectively promoted the development of collateral vessels (VEGF vs bFGF).1.Appropriate control of the ex vivo gene therapyWe injected various numbers of gene (bFGF)-transduced fibroblasts (5x10^5 cells, 1x 10^6 cells, 5x10^6 cells and 1x10^7 cells) to the rabbit model of hind limb ischemia, and evaluated angiogenic effects at 28 days after intra-arterial administration. There were no significant effects in the rabbits treated with 5x10^5 cells nor 1x 10^6 cells. In the animals treated with 5x10^6 cells or 1x10^7 cells significant improvement of tissue perfusion was observed, though abundant cells were distributed to lung after injection of 1x10^7 cells. These findings indicated that 5x10^6 was appropriate number of cell administration.2.VEGF vs bFGFThe auto-fibroblasts, which were transferred with VEGF gene (VEGF group) or bFGF gene (bFGF group), were injected to rabbit ischemic limb in the same manner. Twenty-eight days after the treatment, collateral conductance and angiographic score in the bFGF group was significantly higher than those in the VEGF group, while no significant difference was detected in calf blood pressure ratio and capillary density between the bFGF and VEGF groups. These data suggested that bFGF promoted arteriogenesis as compared with VEGF.

以前，我们开发了用于治疗缺血性四肢的新型血管生成疗法，其中将自身成纤维细胞（用修饰的BFGF基因转导的腺苷酸脂肪细胞）被注入缺血性肢体thorugh thorugh一种动脉内导管（EX VIVO方法）。 In the present study, we determined (1)how many gene-transduced fibroblasts induced appropriate therapeutic effects and (2)which angiogenic growth factor effectively promoted the development of collateral vessels (VEGF vs bFGF).1.Appropriate control of the ex vivo gene therapyWe injected various numbers of gene (bFGF)-transduced fibroblasts (5x10^5 cells, 1x 10^6细胞，5x10^6细胞和1x10^7细胞）到后肢缺血的兔模型，并在动脉内给药后28天评估了血管生成作用。用5x10^5细胞和1x 10^6细胞处理的兔子没有显着影响。在用5x10^6细胞或1x10^7细胞处理的动物中，观察到组织灌注的显着改善，尽管注射1x10^7细胞后，大量细胞分布在肺部。这些发现表明5x10^6是适当的细胞给药数。治疗后的28天，BFGF组的侧外导和血管造影评分明显高于VEGF组的侧支电导率和血管造影评分，而BFGF和VEGF组之间的CALF血压比和毛细管密度没有发现显着差异。这些数据表明，与VEGF相比，BFGF促进了动脉生成。