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

用基因工程血管内皮细胞（ECs）播种假体移植物提供了增强其抗血栓性的潜力。研究了犬扩展聚四氟乙烯（ePTFE）移植物上腺病毒htpa转导的内皮细胞的保留情况和tPA分泌功能。我们的研究结果表明，过表达的tPA在短时间内对种子ECs的保留影响不大。较短的离体培养时间有利于内皮细胞在假体上的体内保留。在体外实验中，将人血栓调节蛋白基因引入内皮细胞，可显著提高细胞的抗血栓活性。然而，将这种转基因内皮细胞植入ePTFE移植物，当移植到猴子髂外静脉时，没有表现出比对照移植物更好的通畅性。目前，能够评估转基因内皮细胞体内功能的系统正在发展，以排除移植所伴随的技术问题。将碱性成纤维细胞生长因子（bFGF）基因导入成纤维细胞，并将其移植到缺血肢体中，可促进肢体血管生成。该方法可为肢体缺血的治疗提供一种新的策略。

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.