神经干细胞复合功能化注射型胶原支架用于脊髓损伤的修复及实时监测

项目名称： 神经干细胞复合功能化注射型胶原支架用于脊髓损伤的修复及实时监测

项目编号： No.81501074

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 沈贺

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： 19万元

中文摘要： 脊髓损伤是一种难修复治疗的中枢神经系统疾病。目前，干细胞治疗被认为是解决这一难题的新策略。但是，移植后干细胞的存活和向神经元分化容易因损伤病理微环境而受到抑制。因此，如何构建适宜的移植微环境是提高神经干细胞在体内存活、增殖和分化能力的关键。本项目拟制备可注射的基于胶原的温敏性水凝胶材料，复合神经干细胞后可直接注射至损伤部位形成支架。同时，将材料与生长因子和神经分化抑制因子拮抗剂修饰的Fe3O4纳米粒子结合，构建具有磁共振成像的功能支架材料，期望利用生长因子和阻断神经分化抑制因子的EGFR抗体提供利于神经再生的微环境，促进神经损伤修复。在此基础上，利用磁共振成像技术实时提供支架在体内的状态信息。通过本项目的实施为发展利用适宜的微环境和神经干细胞治疗脊髓损伤提供理论依据和技术支持。

中文关键词： 脊髓损伤；神经干细胞；注射型胶原支架；微环境；磁共振成像

英文摘要： Spinal cord injury (SCI) is a serious central nervous system (CNS) trauma that could hardly be successful repaired. Recently, strategy of combining scaffolds with neural stem cells (NSCs) offers a promising approach of SCI treatment. However, the main challenge for NSC-mediated repair is lack of favorable environment to direct NPCs differentiation towards neurons rather than glial cells. The myelin associated inhibitors and EGFR activity at the lesion site have been demonstrated to promote NSC differentiation into glial lineage. To promote axonal regeneration after injuries in CNS, an environment suitable for NSC growth and differentiation is critical. Hence, we propose here that using thermo-sensitive collagen-based polymer as scaffolds combined with NSCs for axonal regeneration, which can be directly injected to the damage site. To enhance neurotrophic effects, nerve growth factor and EGFR inhibitor modified Fe3O4 nanoparticles are explored to functionalize the injectable collagen scaffold for NSC implantation. The synthesized scaffold with magnetic resonance imaging (MRI) functionality provides proper microenvironment for NSC growth and differentiation, as well as offers real-time status of the implanted scaffold in vivo using MRI. The present work will provides an insight into a rational design of new injectable scaffolds with growth factor and MRI functionality, and therefore creating appropriate microenvironment for NSC regulation, which will provide valuable information for clinical use of NSCs.

英文关键词： spinal cord injury;neural stem cell;injectable collagen scaffold;microenvironment;magnetic resonance imaging