脂肪干细胞来源的神经前体细胞移植治疗脑出血及其机制研究

项目名称： 脂肪干细胞来源的神经前体细胞移植治疗脑出血及其机制研究

项目编号： No.81471201

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 唐洲平

作者单位： 华中科技大学

项目金额： 80万元

中文摘要： 目前对脑出血患者的神经功能康复尚无有效的治疗方法。脂肪干细胞可被诱导分化为神经前体细胞，移植后在脑内具有多向分化和再生神经元的能力，且具有易大量获取、可自体移植、无免疫排斥反应、不涉及伦理学问题等优势。本项目拟采用携带绿色荧光蛋白基因的慢病毒转染大鼠脂肪干细胞，在体外特定条件下将其诱导分化为神经前体细胞，通过立体定向注射将其移植到脑出血模型大鼠侧脑室内，观察大鼠神经功能恢复情况；采用国际首创的显微光学切片断层成像系统（MOST：可清晰显示全脑神经元三维网络结构，骆清铭等，Science，2010），观察移植细胞在脑内的存活、增殖、迁移和分化，并进一步研究其可能的作用机制：减轻早期炎症反应，减少神经细胞死亡，外源性神经发生和突触形成，促进内源性神经、血管发生等。本项目旨在探索脂肪干细胞来源的神经前体细胞移植对于脑出血的治疗效果及其作用机制，为进一步的临床应用提供切实可靠的科学依据。

中文关键词： 脂肪干细胞；神经前体细胞；细胞移植；脑出血；机制

英文摘要： There hasn't been any curative and effective method for intracerebral hemorrhage (ICH). Adipose-derived stem cells (ADSCs) can be differentiated into neural precursor cells (NPCs) in vitro under a particular condition. NPCs have the abilities of multidifferentiation and neuron reborn. Moreover, ADSCs derived NPCs are easily available, can be used in autotransplantation, and have no immunological rejection or ethical considerations. In this project, rat ADSCs, infected by a lentivral vector-encoding green fluorescent protein (GFP), will be induced to differentiate into NPCs in vitro. Then these NPCs will be transplanted into the lateral ventricle of ICH model rats using stereotactic injection. The improvement of neurological function of rats will be compared. The survival, proliferation, migration and differentiation of transplanted cells will be traced by the micro-optical sectioning tomography (MOST) system. The involving mechanisms will be investigated, which may be related to lightening inflammatory response at the early stage, reducing neuronal cell death, exogenous neurogenesis and synapse formation, and promoting endogenous neurogenesis and angiogenesis. In conclusion, this project is aiming at investigating the therapeutic effect and the mechanism of ADSCs derived NPCs transplantation in ICH model rats, which may provide reliable scientific basis for further clinical application.

英文关键词： adipose-derived stem cells;neural precursor cells;cell transplantation;intracerebral hemorrhage;mechanism