Gene delivery approaches to vascular graft elastogenesis

血管移植物弹性发生的基因传递方法

• 批准号: 7054452
• 负责人: Marsha W ROLLE
• 金额: $ 4.88万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-22 至 2007-03-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054452
• 关键词: antisense nucleic acid; bioreactors; biotechnology; blood vessel transplantation; cell proliferation; collagen; crosslink; elastic tissue; elasticity; elastin; gene delivery system; molecular assembly /self assembly; postdoctoral investigator; proteoglycan; tensile strength; tissue /cell culture; tissue engineering; tissue support frame; vascular smooth muscle

DESCRIPTION (provided by applicant): Among the primary obstacles to generating tissue engineered blood vessels (TEBV) is the inability of seeded cells to produce sufficient amounts of cross-linked elastin to achieve the mechanical characteristics of normal arteries. The objective of this proposal is to optimize conditions for adult smooth muscle cell proliferation, alignment and elastogenesis to achieve rapid development of TEBV in culture. A genetic engineering strategy based on overexpression of a splice variant of the proteoglycan versican, V3, induces elastogenesis in adult mammalian cells both in vitro and in vivo, but attenuates cell proliferation. The objectives of this proposal are to generate regulatable vectors for expression of V3 and other elastogenic genes so that the magnitude and timing of elastin synthesis can be controlled. We hypothesize that this system will enable optimization of cell coverage and elastin deposition on biomaterial scaffolds. To provide mechanical support and promote alignment, cells will be seeded onto grooved collagen membranes. Sheets of aligned cells will be formed into tubular constructs. The constructs will be subjected to radial strain in a bioreactor and the mechanical contribution of cell pre-alignment and elastogenesis will be assessed.

描述（由申请人提供）：产生组织工程血管（TEBV）的主要障碍之一是种子细胞无法产生足够量的交联弹性蛋白以实现正常动脉的机械特性。该提案的目的是优化成体平滑肌细胞增殖、排列和弹性生成的条件，以实现 TEBV 在培养物中的快速发育。基于多功能蛋白聚糖 V3 剪接变体过度表达的基因工程策略，可在体外和体内诱导成年哺乳动物细胞的弹性生成，但会减弱细胞增殖。该提案的目标是生成用于表达 V3 和其他弹性蛋白基因的可调节载体，以便可以控制弹性蛋白合成的程度和时间。我们假设该系统将能够优化生物材料支架上的细胞覆盖和弹性蛋白沉积。为了提供机械支撑并促进排列，细胞将被接种到有凹槽的胶原膜上。对齐的细胞片将形成管状结构。该构建体将在生物反应器中受到径向应变，并且将评估细胞预排列和弹性生成的机械贡献。