神经干细胞复合顺序释放生长因子的胶原海绵修复脊髓损伤

项目名称： 神经干细胞复合顺序释放生长因子的胶原海绵修复脊髓损伤

项目编号： No.81200963

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 李晓然

作者单位： 中国科学院苏州纳米技术与纳米仿生研究所

项目金额： 24万元

中文摘要： 脊髓损伤修复是临床医学重大难题。神经干细胞复合支架提供了新途径，促进其存活、增殖和向神经元分化是焦点问题。表皮细胞生长因子(EGF)可促进神经干细胞增殖，脑源性神经营养因子(BDNF)可促进其向神经元分化、轴突再生，但二者同时使用效果不理想，传统培养通常顺序使用含EGF和BDNF的培养基，但不适于体内植入，本项目拟建立支架担载EGF、BDNF顺序释放体系，期望促进神经干细胞先存活、增殖，再向神经元分化、轴突再生。为了实现顺序释放，改造生长因子，将从胶原酶中筛选的与胶原结合的功能短肽(CBD)与BDNF融合，课题组前期已证实CBD-BDNF与胶原涂层结合实现了延缓释放。研究胶原海绵支架担载EGF和CBD-BDNF顺序释放动力学，对神经干细胞增殖、分化的作用，以及神经干细胞复合此支架对大鼠脊髓全横断损伤修复效果。通过本研究可望建立顺序释放新方法，加深对神经干细胞调控的认识，为临床应用基定基础。

中文关键词： 脊髓损伤；胶原海绵支架；功能化修饰；神经干细胞；定向分化

英文摘要： There is no effective treatment for neurological deficits resulting from spinal cord injury (SCI) despite significant medical and surgical advances. The combined strategy with neural stem cells (NSCs) and scaffolds offers a promising approach to promote SCI recovery. Creating a permissive environment in vivo to improve neural stem cell survival and neural differentiation is becoming increasingly attractive. Epidermal growth factor (EGF) is known to promote proliferation of NSCs in vitro culture, as well as in vivo environments. Brain-derived neurotrophic factor (BDNF) is of particular interest with regards to directing cell fate toward neuronal specification, and promoting neuronal survival, synaptogenesis, and axonal regeneration. However, the simultaneous use of EGF and BDNF can not achieve an excellent synergistic effect. In traditional culture system, NSCs were expanded and maintained in an undifferentiated state in medium supplemented with EGF, after a certain time, the medium was changed with BDNF to induce neuronal differentiation. However, it is not suitable for in vivo implantation. We propose here a strategy based on sequential delivery of EGF and BDNF from collagen sponges to promote NSC survival and proliferation, and then neuronal differentiation and axon regeneration. In order to achieve the sequen

英文关键词： Spinal cord injury；Collagen sponge；Functionalization；Neural stem cell；Directed differentiation