Growth factor gene mediated cartilage repair

描述(由申请人提供)：拟议研究的目的是开发和验证一种基因治疗方案，用于持续局部释放胰岛素样生长因子-I(IGF-I)，释放的数量足以促进马关节软骨的愈合。IGF-I在软骨发育和动态平衡中起着重要的作用，先前的研究表明IGF-I可以促进实验性损伤软骨的愈合。然而，一个重要的限制是无法在损伤部位维持治疗水平的IGF-I。为了克服这一限制，我将使用腺病毒载体将IGF-I基因结构引入马的软骨细胞。然后，将转基因细胞导入到实验损伤的关节中，并以预定的间隔检查产生的修复组织。此后，我将评估供体细胞的存活情况，并量化局部IGF-I基因的表达，将其与反映愈合过程各个方面的生物力学、分子生物学、组织学和生物力学分析相关联。

DESCRIPTION (provided by applicant): The aim of the proposed research is to develop and validate a gene therapy protocol for the sustained local release of Insulin-Like Growth Factor-I (IGF-I) in amounts sufficient to promote healing of equine articular cartilage. IGF-I has an important role in cartilage development and homeostasis, and in previous studies has been shown to promote healing in experimentally injured cartilage. An important limitation, however, has been the inability to sustain therapeutic levels of IGF-I at the site of injury. To overcome this limitation, I would use an adenovirus vector to introduce an IGF-I gene construct into equine chondrocytes. The transfected cells would then be imported into experimentally injured joints, with the resulting repair tissue examined at predetermined intervals. Thereafter, I would assess donor cell survival and quantify local IGF-I gene expression, correlations being drawn with biomechanical, molecular biological, histological and biomechanical analyses that reflect various aspects of the healing process.