Development of hybrid-type vascular prosthesis with application of gene transfer technique

应用基因转移技术开发混合型人工血管

• 批准号: 08557068
• 负责人: MIYATA Tetsuro
• 金额: $ 6.78万
• 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 (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557068/
• 关键词: small caliber vascular prosthesis; hybrid-type vascular prosthesis; endothelial cell; thrombomodulin; plasminogen activators; tissue plasminegen activator; thrombomonodulin; 遺伝子治療; adenovirus; 血管内皮細胞; 小口径人工血管; PDGF

Seeding of prosthetic grafts with genetically engineered vascular endothelial cells (ECs) provides the potential to enhance its antithromboticity. The retention of adenovirally htPA-transduced ECs seeded on expanded polytetrafluoloethylene (ePTFE) grafts and the function of tPA secretion in the canine model was examined. Our results suggest that overexpressed tPA makes little effect on the retention of seeded ECs in a short period. Shorter ex-vivo culture periods is the advantage to the in vivo retention of the ECs on the prosthesis.Introduction of the human thrombomodulin gene to the ECs could greatly enhance the antithrombotic activity of the cells in vitro. However, ePTFE grafts seeded with this genetically modified ECs, when transplanted to the external iliac vein of monkey, failed to show the superior patency over the control grafts. Now the system which enable to evaluate the in-vivo function of the genetically modified ECs is developing to exclude the technical problem accompanying the graft implantation.Introduction of the basic fibroblast growth factor (bFGF) gene to fibroblasts and seeding the cells to the ischemic limb in the rabbi, could enhance the angiogenesis in the limb. This method could be lead to the development of a new strategy of treatment of the ischemic limb.

具有基因工程血管内皮细胞（ECS）的假体移植物的播种提供了增强其抗血栓性的潜力。检查了腺病毒htpa转移的EC在膨胀的聚氟乙烯（EPTFE）移植物上的播种，并检查了TPA分泌在犬模型中的功能。我们的结果表明，过表达的TPA在短时间内对播种EC的保留几乎没有影响。较短的活体培养期是EC在体内保留在假体中的优势。人类血栓形成蛋白基因对ECS的引入可能会极大地增强细胞体外细胞的抗栓性活性。然而，当移植到猴子外部静脉时，Eptfe移植物与这种转基因的EC播种，未能显示出对对照移植物上的优质通畅性。现在，能够评估遗传修饰的EC的体内功能的系统正在开发，以排除伴随移植植入的技术问题。介绍基本成纤维细胞生长因子（BFGF）基因（BFGF）基因对成纤维细胞，并将细胞播种到rabbi中的细胞中，可以增强血管生成。这种方法可能导致发展新的缺血肢体治疗策略。

项目成果

宮田哲郎: "人工臓器と生体材料" 外科. 61. 149-152 (1999)

Tetsuro Miyata：“人造器官和生物材料”外科。 61. 149-152 (1999)

Miyata.T: "A lipoplotein lipase activator, No-1886 improves endothelium-dependent relaxation of rat asrta associated urth aguing" Europ.J.Pharmacol.350. 75-79 (1998)

Miyata.T：“一种脂蛋白脂肪酶激活剂，No-1886 可改善与尿道炎相关的大鼠 asrta 的内皮依赖性松弛”Europ.J.Pharmacol.350。

宮田 哲郎: "遺伝子導入法の血管外科への応用" 外科. 60. 1680-1684 (1998)

Tetsuro Miyata：“基因转移方法在血管外科中的应用” Surg. 60. 1680-1684 (1998)

Sugawara Y et al.: "Rapid posfincubation endothelial retention by Dacron grafts" J.Surg.Res.67. 132-136 (1997)

Sukawara Y 等人：“通过涤纶移植物快速保温后内皮保留”J.Surg.Res.67。

Hara Tsutomu, Kusunoki Masataka, Tsutsumi Kazuhiko, Okada Kazuko, Sakamoto Sadaichi, Ohnaka Masaharu, Nakamura Takao, Miyata Tetsuro, Nakayama Kaori, Fukatsu Atsushi, Kato Katsumi, Kakumu Shinichi, Nakaya Yutaka: "A lipoprotein lipase activator, NO-1886,

原勉、楠木正孝、堤和彦、冈田和子、坂本贞一、大中正治、中村隆夫、宫田哲朗、中山香织、深津厚、加藤克己、角武真一、中谷裕：“脂蛋白脂肪酶激活剂，NO-1886，