磁性三维纳米阵列调控神经干细胞定向分化为螺旋神经元及新生神经突定向生长作用研究

Neurosensory deafness is induced by irreversible loss of cochlear hair cells and spiral ganglion neurons. Regeneration of functional spiral ganglion neurons through transplanting neural stem cells has become a researching focus in nowadays, and the key factor is how to promote neural stem cells differentiating into functional spiral ganglion neurons, nascent neurites orientated growth and linking with cochlear hair cells in final. Our previous study indicated that static magnetic field, one-dimensional nanostructure could regulate neural stem cells differentiating into spiral ganglion neurons effectively, and graphene could promote neurites growth. This project sets up an unified magnetic three-dimensional nanostructure array system(UMTNAS) by integration of static magnetic field, one-dimensional nanostructure and graphene; studies the regulating effect of static magnetic field and UMTNAS on differentiation of neural stem cells into spiral ganglion neurons; and researches the oriented growth of nascent neurites. We propose to achieve the following aims, Aim1: setting up the UMTNAS successfully; Aim2: studying the regulating effect of the UMTNAS on neural stem cells differentiating into spiral ganglion neurons, and the growth of nascent neurites; Aim3: studying the oriented growth of nascent neurites induced by the UMTNAS under oriented static magnetic field. This project will lay the theory and experiment foundations of clinical treatment on neurosensory deafness.

感音神经性聋是由耳蜗毛细胞和螺旋神经元不可逆损失导致的,通过干细胞移植再生螺旋神经元是目前的研究热点，其中最为关键的科学问题是如何促进干细胞分化为有功能的螺旋神经元,并促使新生螺旋神经元神经突定向生长并分布到耳蜗毛细胞上。我们的前期研究表明静态磁场刺激、一维纳米结构能够有效调控神经干细胞定向分化为神经元，并且石墨烯材料能够促进神经突生长。本项目通过集成静态磁场刺激、一维纳米结构、石墨烯神经界面材料为一体化磁性三维纳米阵列装置，研究磁场及磁性三维纳米阵列调控神经干细胞分化为螺旋神经元，及新生神经元神经突生长的规律。拟实现以下目标：一、搭建并优化磁性三维纳米阵列；二、研究磁性三维纳米阵列调控神经干细胞分化为螺旋神经元及促进神经突生长的规律；三、研究磁性三维纳米阵列在定向磁场中调控新生螺旋神经元神经突定向生长的规律。本项目将为通过干细胞移植再生螺旋神经元治疗耳聋奠定理论和实验基础。

本项目以干细胞移植再生听觉神经元，修复听觉神经通路，治疗感音神经性聋为背景，综合集成了神经干细胞，磁性生物材料，生物相容性水凝胶材料等因素。设计并构建了磁性纳米线三维诱导体系，通过此磁性三维诱导体系诱导神经干细胞定向分化，听觉神经元定向生长。通过本项目，我们实现了通过磁性三维诱导体系，促进神经干细胞定向排列，新生神经元定向生长等关键细胞行为的调控；实现了通过磁性三维诱导体系促进螺旋神经元细胞定向排列，多方向诱导生长，功能成熟等听觉神经元细胞的关键细胞行为和细胞生理功能的调控；实现了通过RNA-seq技术检测“接触-诱导”这一物理因素调控螺旋神经元细胞定向迁移，定向排列，生长锥生长，突触蛋白生长等关键细胞行为的作用机制。本项目为通过基于干细胞移植治疗感音神经性聋提供了重要的技术支持和实验基础。