EPC Adhesion to Teflon-AF and ePTFE Vascular Grafts

EPC 对 Teflon-AF 和 ePTFE 血管移植物的粘附

• 批准号: 7848575
• 负责人: William Montgomery Reichert
• 金额: $ 1.03万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7848575
• 关键词: Academic Medical Centers; Address; Adenoviruses; Adherence; Adhesions; Adult; Allografting; Animal Model; Animal Testing; Arteries; Autologous; Binding; Biocompatible Materials; Biological Assay; Biomedical Engineering; Blood; Blood Platelets; Blood Vessels; Blood flow; Bypass; CD31 Antigens; Caliber; Cardiac Catheterization Procedures; Cell Adhesion; Cell Shape; Cell physiology; Cells; Clinical; Collaborations; Coronary Arteriosclerosis; Coronary Artery Bypass; Cultured Cells; Diagnostic; Doctor of Philosophy; Elasticity; Endothelial Cells; Endothelin; Endothelin-1; Endothelium; Enzyme-Linked Immunosorbent Assay; Epoprostenol; Exposure to; Family suidae; Fibronectins; Film; Future; Gene Expression; Genes; Goals; Growth; Harvest; Health; Histology; Human; Hyperplasia; Image; Immunohistochemistry; In Situ; In Vitro; Integrins; Laboratories; Legal patent; Leukocytes; Ligands; Maintenance; Measures; Mechanics; Mediating; Modeling; Nitric Oxide; Nude Rats; Operative Surgical Procedures; PTGS2 gene; Patients; Photography; Postdoctoral Fellow; Procedures; Prostaglandins I; Proteins; Protocols documentation; Rattus; Research; Series; Serum; Shapes; Smooth Muscle; Solutions; Source; Staining method; Stains; Stem cells; Surgeon; System; Teflon; Testing; Thick; Thrombomodulin; Thrombosis; Thrombus; Time; Tissues; Transfection; Trypsin; Umbilical Cord Blood; VWF gene; Vascular Endothelial Growth Factors; Vascular Graft; Veins; Venous; Western Blotting; Work; Xenograft procedure; acetyl-LDL; cellular imaging; clinical application; clinically significant; femoral artery; healthy volunteer; implantation; improved; in vitro testing; in vivo; innovation; novel; peripheral blood; professor; public health relevance; research study; response; shear stress; success; tool

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.

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品，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（<6mm）动脉或静脉的替代品。这种替代品的缺乏是由于腔内血栓形成和新内膜增生堵塞了替代小直径血管。在小直径血管移植物的管腔中生长一层完整的内皮是提高移植物通畅性的一种有前途的方法。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) ECs 的自体来源，(2) ECs 层在移植物管腔上的附着、生长和保留，以及 (3) ECs 层的抗血栓特性的维持。此次竞争性更新的具体目的是（1）确定从患有冠状动脉疾病的成人的外周血中分离出可靠且可行的血源性自体 EPC 来源，（2）用人血栓调节蛋白（hTM）基因转染 EPC，（3）验证接种到的天然和 hTM 转染 EPC 中抗血栓标志物的粘附和表达 Teflon AF 血管移植替代膜，(4) 验证铺在直径 1 mm ePTFE 血管移植物内腔上的天然和 hTM 转染 EPC 中抗血栓标记物的粘附和表达，以及 (5) 在裸鼠中测试铺有天然或 hTM 转染 EPC 的 ePTFE 移植物的短期通畅性。将研究人类 EPC 以期待未来的临床应用。公众健康相关性：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替代品，但没有临床上可接受的健康自体小直径（<6mm）动脉或静脉的替代品。我们建议，在合成的小直径 ePTFE 血管移植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可行的替代方案。