CXCL12通过增强细胞间通讯调控神经血管单元促进脊髓损伤修复

项目名称： CXCL12通过增强细胞间通讯调控神经血管单元促进脊髓损伤修复

项目编号： No.91739115

项目类型： 重大研究计划

立项/批准年度： 2018

项目学科： 医药、卫生

项目作者： 许东升

作者单位： 同济大学

项目金额： 20万元

中文摘要： 急性脊髓损伤是较多发生的难治的重大创伤，其功能康复依赖于损伤神经的修复和功能重建。目前神经修复和神经调控手段取得了初步的疗效，但多数效果非常有限。间充质干细胞（MSC）移植已经在多个临床试验中应用，MSC除免疫调节功能之外，是否调控神经血管单元（Neuovascular unit，NVU）的形成和功能，尚未受到重视。申请人既往对MSC的重要旁分泌因子，趋化因子CXCL12进行多年的研究。本课题旨在通过观察CXCL12对NVU的作用，揭示这一重要细胞因子对血管重建和神经修复的重要意义。本课题将回答以下科学问题：1）CXCL12定向调控NVU的形成与重建；2）内皮细胞（EC）与内源性神经干细胞（NPC）通过外泌体的细胞间通讯促进NVU形成。

中文关键词： 脊髓损伤；CXCL12；神经血管单元；细胞间通讯；外泌体

英文摘要： Acute spinal cord injury (SCI) is a major refractory trauma with high incidence. Its functional rehabilitation depends on the repair and functional reconstruction of the injured nerve. At present, neurological rehabilitation and neuromodulation have achieved initial efficacy, but most of them are very limited. Mesenchymal stem cell （MSC）transplantation has been used in several clinical trials，and in addition to regulate immune function, function and the mechanism of regulation of the neurovascular unit（NVU）, there is no attention. On the other hand, angiogenesis plays an critical role in the process of nerve repair.It is important that the new endothelial cells （EC）communicate with the cells of the endogenous neural stem cells（NPC）for NVU. Our previous studies have investigated the important paracrine factor chemokine CXCL12 for many years. The purpose of this study is to investigate the key function in vascular remodeling and neural repair by observing the efforts of CXCL12 in NVU. This project will answer the following scientific questions: 1) CXCL12 initiately regulates formation and functional reconstruction of NVU; 2) in vitro tissue or animal model， cell communication between EC and NPC promotes NVU through EC exosomes.

英文关键词： Spinal cord injury;CXCL12; Neurovascular unit;Cell communication;Exosome