Diabetes Resistant Vascular Graft Remodeling

抗糖尿病血管移植重塑

• 批准号: 8742738
• 负责人: Agneta Simionescu
• 金额: $ 19.69万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8742738
• 关键词: Abattoirs; Adipose tissue; Adult; Advanced Glycosylation End Products; Affect; Anastomosis - action; Animal Model; Animals; Antioxidants; Arterial Medias; Atherosclerosis; Autologous; Binding; Biochemical; Biomedical Engineering; Bioreactors; Blood Glucose; Blood Vessels; Caliber; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell Separation; Cells; Centers of Research Excellence; Characteristics; Clinical; Collagen; Complex; Complications of Diabetes Mellitus; Data; Diabetes Mellitus; Elastin; Engineering; Environment; Extracellular Matrix; Family suidae; Fibrosis; Funding; Future; Glucose; Goals; Impaired wound healing; Implant; In Vitro; Inflammation; Life; Mechanics; Medial; Mentors; Modeling; Molecular; Monitor; Natural regeneration; One-Step dentin bonding system; Pathology; Patients; Pentas; Performance; Peripheral; Peripheral arterial disease; Process; Property; Proteins; Publishing; Research; Resistance; Risk Factors; Scientist; Stabilizing Agents; Stem cells; Stimulus; Streptozocin; Testing; Tissue Engineering; Tissues; Translations; Tunica Adventitia; Vascular Diseases; Vascular Graft; abdominal aorta; base; bioimaging; calcification; crosslink; diabetic; diabetic patient; diabetic rat; endothelial dysfunction; expectation; glucose metabolism; implantation; internal thoracic artery; lipid metabolism; novel; polyphenol; preclinical evaluation; protective effect; scaffold; type I diabetic; vascular tissue engineering; vessel regression

Project Summary Diabetes is a major risk factor for cardiovascular diseases, and vascular stiffening and calcification are considered the hallmark of diabetes. Therefore there is a major need for engineered vascular grafts with long- term patency and durability to be used in diabetic cardiovascular patients. Tissue-engineered constructs based on collagen and elastin scaffolds and autologous progenitor cells hold great promise to treat vascular diseases, but very little information exists regarding their fate in the diabetic environment. The altered glucose and lipid metabolism characteristic of diabetes results in endothelial dysfunction, accelerated atherosclerosis, activation of inflammation, and fibrosis and impaired healing, all of which are not conducive to the desired integration and remodeling of tissue engineered constructs. The long-term goal of this research is to develop viable tissue-engineered vascular substitutes adapted to withstand diabetes-related complications. The hypotheses, robustly supported by preliminary data, are that both matrix and cells are affected in a diabetic milieu and that treatment of collagen- and elastin-based scaffolds with polyphenols would protect the matrix from stiffening and calcification. To test these hypotheses, adipose derived stem cell-seeded vascular scaffolds will be implanted in type 2 diabetic rats as direct end-to- end anastomoses in the abdominal aorta, and their remodeling and survival will be investigated (Aim 1). To mitigate diabetes-induced alterations, the scaffolds will be treated with polyphenol stabilizing agents prior to cell seeding, and the grafts will be implanted in diabetic rats (Aim 2). Expertise of the PI's scientist mentor, Dr. Vyavahare, PI of this COBRE, and clinical mentor, Dr. Langan, are greatly relevant to the project; core support for stem-cell isolation and characterization and bioimaging of vascular scaffold in animals is essential for this project to succeed. Typically, tissue-engineered constructs and their remodeling are tested in healthy animals for preclinical evaluation. Using a diabetic animal model will provide new information about the molecular mechanisms of this pathology and the fate of collagen- and elastin-based scaffolds in a diabetic environment. Treatment of tissue- derived vascular scaffolds with polyphenols will eventually protect them from diabetic complications and support their future use for cardiovascular tissue engineering in diabetic patients.

项目摘要 糖尿病是心血管疾病的主要危险因素，血管僵硬和钙化是 被认为是糖尿病的标志。因此，需要长长的工程血管移植 在糖尿病心血管患者中使用的术语通畅和耐用性。基于组织工程的结构 在胶原蛋白和弹性蛋白支架以及自体祖细胞上，有很大的希望治疗血管疾病， 但是，在糖尿病环境中有关其命运的信息很少。葡萄糖和脂质改变 糖尿病的代谢特征会导致内皮功能障碍，加速动脉粥样硬化，激活 炎症，纤维化和愈合受损，所有这些都不有利于所需的整合和 组织工程结构的重塑。 这项研究的长期目标是开发适合于 承受与糖尿病有关的并发症。由初步数据强烈支持的假设是 基质和细胞在糖尿病环境中都受到影响，并且基于胶原蛋白和弹性蛋白的处理 带有多酚的脚手架可以保护基质免受僵化和钙化。为了检验这些假设， 脂肪衍生的干细胞种子血管支架将植入2型糖尿病大鼠 在腹主动脉中结束吻合，将研究其重塑和生存（AIM 1）。到 减轻糖尿病诱导的改变，脚手架将用多酚稳定剂处理 细胞播种，移植物将植入糖尿病大鼠（AIM 2）。 PI科学家的专业知识，博士 该山co的PI和临床导师Langan博士Vyavahare与该项目非常相关。核心支持 对于干细胞的隔离和表征和动物血管支架的生物成像至关重要 成功的项目。 通常，在健康动物中测试了组织设计的构建体及其重塑的临床前 评估。使用糖尿病动物模型将提供有关此分子机制的新信息 在糖尿病环境中，病理学以及基于胶原蛋白和弹性蛋白的脚手架的命运。组织的处理 带有多酚的衍生血管支架最终将保护它们免受糖尿病并发症的影响 支持他们未来用于糖尿病患者心血管组织工程的使用。