EPC Adhesion to Teflon-AF and ePTFE Vascular Grafts

描述（由申请人提供）：虽然有许多自体大直径血管移植物的手术替代方案，即同种异体移植物、异种移植物和合成血管移植物替代品，但没有临床上可接受的健康自体小直径（<6 mm）动脉或静脉的替代方案。替代血管的缺乏是由于管腔血栓形成和新生内膜增生导致替代小直径血管闭塞。在小直径血管移植物的管腔中生长一层完整的内皮是增加移植物通畅性的一种有希望的方法。在本研究中，我们假设体外内皮化小直径ePTFE血管移植物的临床成功取决于三个相互作用因素的融合：（1）EC的自体来源，（2）EC层与移植物管腔的附着、生长和保留，以及（3）EC层维持抗血栓形成特征。该竞争性更新的具体目的是（1）鉴定从患有冠状动脉疾病的成人外周血中分离的血液来源的自体EPCs的可靠和可行来源，（2）用人血栓调节蛋白（hTM）基因转染EPCs，（3）验证接种在Teflon AF血管移植物替代膜上的天然和hTM转染EPCs中抗血栓标记物的粘附和表达，（4）验证在1mm直径的ePTFE血管移植物的管腔上的天然和hTM转染的EPC中抗血栓标记物的粘附和表达，和（5）在裸大鼠中测试用天然或hTM转染的EPC sodded的ePTFE移植物的短期开放性。人类EPCs将在未来的临床应用的预期进行研究。公共卫生相关性：虽然有许多自体大直径血管移植物的手术替代方案，即同种异体移植物、异种移植物和合成血管移植物替代品，但没有临床上可接受的健康自体小直径（<6 mm）动脉或静脉的替代方案。我们提出，在小直径ePTFE血管移植物合成物的管腔中生长一层完整的自体内皮，将为缺乏合适的健康自体组织的患者提供一种可行的替代方案。

DESCRIPTION (provided by applicant): While there are a number of surgical alternatives to autologous large diameter vascular grafts, i.e. allografts, xenografts, and synthetic vascular graft substitutes, there are no clinically acceptable alternatives to healthy autologous small diameter (<6mm) artery or vein. This lack of alternatives arises from luminal thrombosis and neointimal hyperplasia that occlude the substitute small diameter vessel. Growing a layer of intact endothelium in the lumen of small diameter vascular grafts represents a promising means of increasing graft patency. In this study we hypothesize that the clinical success of in vitro endothelialized small diameter ePTFE vascular grafts is dependent upon the confluence of three interacting factors: (1) the autologous sourcing of ECs, (2) the attachment, growth and retention of the layer of ECs to the graft lumen, and (3) the maintenance of an antithrombotic profile by the layer of ECs. The specific aims of this competitive renewal are to (1) identify a reliable and viable source of blood-derived autologous EPCs isolated from the peripheral blood of adults with coronary artery disease, (2) transfect the EPCs with the gene for human thrombomodulin (hTM), (3) verify the adherence and expression of antithrombotic markers in native and hTM transfected EPCs seeded onto vascular graft surrogate films of Teflon AF, (4) verify adherence and expression of antithrombotic markers in native and hTM transfected EPCs sodded onto the lumen of 1 mm diameter ePTFE vascular grafts, and (5) test short term patency of ePTFE grafts sodded with native or hTM transfected EPC in nude rats. Human EPCs will be studied in anticipation of future clinical applications. PUBLIC HEALTH RELEVANCE: While there are a number of surgical alternatives to autologous large diameter vascular grafts i.e. allografts, xenografts, and synthetic vascular graft substitutes, there are no clinically acceptable alternatives to healthy autologous small diameter (<6mm) artery or vein. We propose that growing a layer of intact, autologous endothelium in the lumen of small diameter ePTFE vascular grafts synthetic would provide a viable alternative for patients who lack suitable healthy autologous tissue.