Novel strategies for promoting CNS repair through manipulation of FGF signalling and heparan sulphate proteoglycans

通过操纵 FGF 信号和硫酸乙酰肝素蛋白聚糖促进 CNS 修复的新策略

• 批准号: MR/K014366/1
• 负责人: Susan Barnett
• 金额: $ 52.98万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK014366%2F1
• 关键词: Novel; strategies; promoting; CNS; repair

One of the major limitations in the repair of the damaged CNS is scarring. This is induced in tissue after injury and involves the brain's major support cell (or glial cell), the astrocyte. One repair strategy for CNS injury is to transplant the patient's own glial cells (harvested from peripheral nerves) into the injury site to promote nerve regrowth. There are two possible candidates for cell transplantation, glia from the nose, olfactory ensheathing cells (OECs) and glia of peripheral nerves, Schwann cells. We have found that Schwann cells, but not OECs, induce astrocytic scarring both in experiments in dishes and animal models of injury. Our recent work has shown that Schwann cells secrete complex sugar molecules that enhance the action of specific growth factors, leading to scarring. OECs do not secrete the same sugar structures and, therefore, do not induce scarring, even though they secrete the growth factors known to influence scarring. We have recently developed a number of approaches. The aim of this application is to exploit this new information by developing and testing novel methods to interfere with complex sugar regulation of growth factor signalling in rat models. If successful, this work will lead to design of strategies to manipulate the inhibitory environment induced in humans after injury and promote CNS repair.

修复受损中枢神经系统的主要限制之一是疤痕。这是在受伤后的组织中诱导的，涉及大脑的主要支持细胞（或神经胶质细胞）——星形胶质细胞。中枢神经系统损伤的一种修复策略是将患者自身的神经胶质细胞（从周围神经收获）移植到损伤部位以促进神经再生。有两种可能的细胞移植候选者：鼻子的神经胶质细胞，嗅鞘细胞（OEC）和周围神经的神经胶质细胞，施万细胞。我们发现，在培养皿实验和损伤动物模型中，雪旺细胞（而非 OEC）会诱导星形细胞疤痕形成。我们最近的工作表明，雪旺细胞分泌复杂的糖分子，增强特定生长因子的作用，从而导致疤痕形成。 OEC 不分泌相同的糖结构，因此不会引起疤痕形成，尽管它们分泌已知会影响疤痕形成的生长因子。我们最近开发了多种方法。本申请的目的是通过开发和测试干扰大鼠模型中生长因子信号传导的复杂糖调节的新方法来利用这一新信息。如果成功，这项工作将导致设计策略来操纵人类受伤后诱导的抑制环境并促进中枢神经系统修复。

项目成果

Myelination: Do Astrocytes Play a Role?

• DOI: 10.1177/1073858412465655
• 发表时间: 2013-10-01
• 期刊: NEUROSCIENTIST
• 影响因子: 5.6
• 作者: Barnett, Susan C.;Linington, Christopher
• 通讯作者: Linington, Christopher

Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface.

硫酸酯酶介导的星形胶质细胞-雪旺细胞界面的操作。

• DOI: 10.1002/glia.23047
• 发表时间: 2017-01
• 期刊: Glia
• 影响因子: 6.2
• 作者: O'Neill P;Lindsay SL;Pantiru A;Guimond SE;Fagoe N;Verhaagen J;Turnbull JE;Riddell JS;Barnett SC
• 通讯作者: Barnett SC