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，用于持续局部释放足以促进马关节软骨愈合的胰岛素样生长因子- i （IGF-I）。igf - 1在软骨发育和体内平衡中起着重要作用，在先前的研究中已被证明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 - 1。为了克服这一限制，我将使用腺病毒载体将igf - 1基因构建物引入马软骨细胞。然后将转染的细胞导入实验损伤的关节中，每隔一段时间检查产生的修复组织。此后，我将评估供体细胞存活并量化局部IGF-I基因表达，并通过生物力学、分子生物学、组织学和生物力学分析得出反映愈合过程各个方面的相关性。

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.