Preclinical Investigation of a Bioengineered Vascular Graft

生物工程血管移植物的临床前研究

• 批准号: 8897878
• 负责人: Guillermo Antonio Ameer
• 金额: $ 41.86万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8897878
• 关键词: Address; Agonist; American; Amputation; Animal Model; Anticoagulants; Atherosclerosis; Autologous; Biomaterials Research; Biomedical Engineering; Blood; Blood Vessels; Bypass; Caliber; Carotid Arteries; Cell Count; Cell Culture Techniques; Cell Differentiation process; Cell Proliferation; Cell Separation; Cells; Citrates; Citric Acid; Clinical; Clinical Trials; Contrast Media; Data; E-Selectin; Elastomers; Endothelial Cells; Endothelium; Engineering; Failure; Family suidae; Glycols; Goals; Hospitals; Human; Hyperplasia; In Vitro; Inflammation; Inflammatory; Investigation; Magnetic Resonance Imaging; Modeling; Monitor; Morbidity - disease rate; Nature; Patient Care; Patients; Peripheral arterial disease; Peroxisome Proliferator-Activated Receptors; Phenotype; Physiological; Pioglitazone; Polytetrafluoroethylene; Procedures; Production; Prosthesis; Protocols documentation; Quality Control; Relative (related person); Reporting; Safety; Smooth Muscle Myocytes; Source; Staging; Stem cells; Thrombosis; Time; United States; Validation; Vascular Graft; acetyl-LDL; base; biomaterial compatibility; cost; cytokine; design; improved; improved functioning; in vivo; innovation; monocyte; mortality; multidisciplinary; novel; novel strategies; patient population; peripheral blood; pre-clinical; preclinical study; public health relevance; response; senescence; uptake

DESCRIPTION (provided by applicant): Blockage of blood vessels due to atherosclerosis is one of the main causes of mortality and morbidity in the United States resulting in 600,000 blood vessel replacement or revascularization procedures each year at a cost of over 1 billion dollars. Unfortunately, autologous grafts are often not an option for as many as one third of patients and synthetic grafts used to replace small-diameter blood vessels have high rates of failure due to thrombosis and neointimal hyperplasia. This proposal will investigate a bioengineering approach to improve the function and safety of synthetic grafts, specifically expanded polytetrafluoroethylene (ePTFE). The overall goal of this proposal is to evaluate whether an endothelial progenitor cells (EPC)-derived bioengineered ePTFE graft is feasible for patients with confirmed peripheral arterial disease (PAD) and to investigate the safety and efficacy of bioengineered grafts in a large animal model. In particular, we will investigate the use of pioglitazone, a peroxisome proliferator-activated receptor ? (PPAR-?) agonist, as a novel strategy to increase EPC colony formation and cell proliferation as patients with PAD have been reported to have reduced EPC numbers with impaired function. During the pre-clinical trials of this proposal we will develop cell isolation and cell-seeding protocols that can be readily adapted for use in the hospital setting. The specific aims are to: 1. assess whether circulating EPCs from patients with PAD are a viable cell source for a cell-based bioengineered vascular graft, and 2. evaluate the safety and efficacy of the bioengineered ePTFE grafts in an atherosclerotic swine carotid artery ePTFE bypass model. Given the widespread nature of atherosclerosis and peripheral artery disease, the innovative approach taken in this proposal is expected to directly improve patient care of millions of Americans. This proposal will allow us to gather the necessary expertise and data to design a clinical trial to assess early stage efficacy of the bioengineered grafts.

描述（由申请人提供）：由于动脉粥样硬化引起的血管阻塞是美国死亡率和发病率的主要原因之一，每年导致60万血管置换或血运重建程序，费用超过10亿美元。不幸的是，对于多达三分之一的患者和用于替代小直径血管的合成移植物中，自体移植物通常是不可行的，这是由于血栓形成和新的增生而导致的较高的失败率。该建议将研究一种生物工程方法，以改善合成移植物的功能和安全性，特别是扩展的聚氟乙烯（EPTFE）。该提案的总体目的是评估内皮祖细胞（EPC）衍生的生物工程EPTFE移植物对于确认的周围动脉疾病（PAD）患者是可行的，并研究了大型动物模型中生物工程移植物的安全性和功效。特别是，我们将研究吡格列酮（一种过氧化物酶体增殖物激活的受体）的使用？ （PPAR-？）激动剂，作为增加EPC菌落形成和细胞增殖的一种新型策略，因为据报道，PAD患者的EPC数量减少了功能受损的EPC数量。在该提案的临床前试验中，我们将开发细胞隔离和细胞种植方案，可以很容易地适用于医院环境。具体目的是：1。评估来自PAD患者的循环EPC是否是基于细胞的生物工程血管移植物的可行细胞来源，以及2。评估动脉粥样硬化猪颈颈颈动脉颈动脉动脉eptfe eptfe旁路模型中生物工程EPTFE移植物的安全性和功效。鉴于动脉粥样硬化和周围动脉疾病的广泛性质，该提案中采用的创新方法有望直接改善数百万美国人的患者护理。该建议将使我们能够收集必要的专业知识和数据来设计临床试验，以评估生物工程移植物的早期效果。