Use of Proteoglycan-Genes to Engineer Vascular Tissue

使用蛋白多糖基因改造血管组织

• 批准号: 6844178
• 负责人: Thomas N Wight
• 金额: $ 6.37万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6844178
• 关键词: biodegradable product; bioengineering /biomedical engineering; biomaterial development /preparation; blood vessel prosthesis; clinical research; collagen; elastic tissue; fibrogenesis; human tissue; laboratory rat; polymers; protein isoforms; proteoglycan; tensile strength; tissue /cell culture; tissue engineering; tissue support frame; vascular smooth muscle

DESCRIPTION (provided by applicant): One of the major limitations in vascular tissue engineering is the failure of the engineered tissue to form functional and intact elastic fibers. Recent work in our laboratory has found that by genetically engineering arterial smooth muscle cells to overexpress a specific isoform of the extracellular matrix proteoglycan, versican, elastic fibers form in vitro and in vivo when the transduced cells are seeded into injured arteries. We hypothesize that this technology can be used to create blood vessel substitutes and vascular grafts with intact and functional elastic fibers. To address this hypothesis, this proposal has the following specific aims: 1. Optimize the gene delivery system so that optimal levels of expression can be achieved in a controlled fashion to maximize elastic fiber formation. 2. Create "sheets" of engineered cells in vitro with intact elastic fibers to be used to form small diametric tubes which exhibit maximal elastogenic properties. 3. Assess the feasibility of seeding engineered cells onto micro-fiber based biodegradable polymer scaffolds wrapped around a frame to create layers of smooth muscle cells interspersed with functional elastic fibers and; 4. Determine if integrating these elastic fiber generating cells into collagen based tubular scaffolds will result in the formation of tubes with appropriate tensile strength and elastogenic properties. The overall goal of this application is to create a vascular medial layer that possesses an appropriate mixture of extracellular matrix components that mimic the natural vessel and contain intact and functional elastic fibers.

描述（由申请人提供）： 血管组织工程的主要局限性之一是工程组织未能形成功能性和完整弹性纤维。 我们实验室的最新工作发现，通过基因工程动脉平滑肌细胞，当将传递的细胞接种到损伤动脉中时，在体外和体内形成了细胞外基质蛋白聚糖，versican，弹性纤维的特异性同工型。 我们假设该技术可用于创建具有完整且功能性弹性纤维的血管替代物和血管移植物。 为了解决这一假设，该提案具有以下特定目的：1。优化基因输送系统，以便可以以受控的方式达到最佳的表达水平，以最大程度地提高弹性纤维形成。 2。在体外创建具有完整弹性纤维的工程细胞的“床单”，用于形成具有最大弹性特性的小型直径管。 3。评估播种工程细胞在基于微纤维的可生物降解的聚合物支架上的可行性，这些聚合物支架包裹在框架周围，以创建散布在功能性弹性纤维的平滑肌细胞层，并且； 4.确定将这些弹性纤维产生细胞的整合到胶原蛋白的管状支架中是否会导致形成具有适当拉伸强度和弹性特性的试管。 该应用的总体目标是创建一个血管内侧层，该层具有适当的细胞外基质组件的混合物，该基质成分模仿天然容器并包含完整和功能性的弹性纤维。