Integrin engineering to promote axon regeneration and Schwann cell migration

整合素工程促进轴突再生和雪旺细胞迁移

• 批准号: G0701518/1
• 负责人: James Fawcett
• 金额: $ 105.09万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701518%2F1
• 关键词: Integrin; engineering; promote; axon; regeneration

After damage to the spinal cord or brain many nerve fibres are cut. In spinal cord injury this means that motor commands from the brain cannot reach muscles, and sensory information from the skin cannot reach the brain. In order to produce a cure the nerve fibres have to be made to regenerate from the injury point back into the spinal cord and up towards the brain. At present nerve fibre regeneration after spinal cord damage does not succeed, due to many factors such as the scar tissue at the injury site that blocks nerve fibre growth. In the scar tissue there is a molecule called tenascin which nerve fibres could use to grow on, but they lack the receptor molecules to interact with tenascin. The project will put the necessary type of receptor molecules (integrins) on the cut nerve fibres, and will make further modifications to the integrins to prevent them being turned off by inhibitory factors in the scar tissue. A second part of the project is to take a cell type called Schwann cells, which can promote nerve fibre growth, and implant them into spinal cord injuries as a bridge over which the regenerating nerve fibres can grow. In order to make it possible for these cells to integrate into the spinal cord they will also have modifications to their surface integrins.

脊髓或大脑受损后，许多神经纤维被切断。在脊髓损伤中，这意味着来自大脑的运动指令无法到达肌肉，来自皮肤的感觉信息无法到达大脑。为了产生治疗，神经纤维必须从损伤点再生回到脊髓，然后向上到大脑。目前，由于许多因素，如损伤部位的瘢痕组织阻碍了神经纤维的生长，脊髓损伤后的神经纤维再生并不成功。在疤痕组织中有一种叫做腱生蛋白的分子，神经纤维可以在其上生长，但它们缺乏与腱生蛋白相互作用的受体分子。该项目将在切断的神经纤维上放置必要类型的受体分子（整合素），并对整合素进行进一步修改，以防止它们被疤痕组织中的抑制因子关闭。该项目的第二部分是采用一种名为Schwann细胞的细胞类型，这种细胞可以促进神经纤维生长，并将它们植入脊髓损伤中，作为再生神经纤维生长的桥梁。为了使这些细胞能够整合到脊髓中，它们也将对其表面整合素进行修饰。