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

用基因工程血管内皮细胞（EC）种植人工血管移植物提供了增强其抗血栓形成能力的潜力。在犬模型中检查了接种在膨胀聚四氟乙烯（ePTFE）移植物上的腺病毒htPA转导的EC的保留和tPA分泌的功能。我们的研究结果表明，tPA过表达在短期内对种子EC的保留影响不大。体外培养时间短有利于内皮细胞在假体上的体内滞留，将人血栓调节蛋白基因导入内皮细胞可显著提高其体外抗血栓活性。然而，当移植到猴的髂外静脉时，接种有这种基因修饰的EC的ePTFE移植物未能显示出优于对照移植物的上级通畅性。目前，转基因内皮细胞的体内功能评价系统正在发展，以排除移植物植入的技术问题，将碱性成纤维细胞生长因子（basicfibroblastgrowthfactor，bFGF）基因导入成纤维细胞，接种于兔缺血肢体，可促进肢体血管新生。这种方法可能导致缺血肢体治疗的新策略的发展。

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.