三维导电支架协同电刺激作用NSCs分化及机制的研究

Recently, studies have found that conductive materials as the new "smart" materials have positive effects on the behavior of neural stem cells (NSCs). The role of conductive scaffolds based on conductive polymers on NSCs has been preliminary studied. However, there are few studies on the synergistic effect of conductive scaffolds in combination with electrical stimulation on the differentiation of NSCs, and the molecular mechanism of conductive scaffolds alone or in combination with electrical stimulation to NSCs differentiation is still unclear. We previously prepared a novel three-dimensional conductive scaffold of poly(3,4-ethylenedioxythiophen)/chitosan/gelatin (PEDOT/Cs/Gel). It is found that the conductive scaffold could promote the differentiation of NSCs into neurons. In this project, we will study the effect of three-dimensional conductive scaffolds combined with electrical stimulation on the differentiation of NSCs, then to reveal the molecular mechanism of conductive scaffolds in combination with electrical stimulation to NSCs differentiation. Our project will first explored the relationship between NSCs differentiation and voltage-gated ion channels, and the signal transduction pathways that may be involved in this process. This project will provide the theoretical and experimental basis for studying conductive scaffolds in combination with electrical stimulation to regulate the differentiation of NSCs in vitro, and it is of great significance for the application of NSCs in neuroregenerative medicine.

导电材料作为一种新型“智能”材料对神经干细胞（NSCs）的行为具有积极作用。基于导电聚合物的导电支架对NSCs的作用已有初步研究，但是导电支架协同外加电刺激进一步作用NSCs分化的研究较少，并且导电支架单独或协同电刺激作用NSCs分化的分子机制也尚不清楚。我们前期制备了基于导电聚合物聚3，4-乙撑二氧噻吩（PEDOT）的新型三维导电支架PEDOT/壳聚糖/明胶（PEDOT/Cs/Gel），发现该导电支架可促进NSCs向神经元分化。本项目将进一步研究PEDOT/Cs/Gel三维导电支架协同电刺激对NSCs分化的调控作用，并揭示导电支架协同电刺激作用NSCs分化的分子机制。首次探索导电支架协同电刺激作用NSCs分化与电压门控离子通道的关系及可能参与的信号传导通路，为研究导电支架协同电刺激体外调控NSCs分化提供理论基础和实验依据，对实现NSCs的定向分化及其神经再生医学应用具有重要意义。

神经干细胞（NSCs）因具有自我更新和多向分化潜能，使其在神经再生领域具有重要的应用。然而NSCs存在自发分化缓慢，且分化方向不可控等问题，这限制了其神经再生应用的安全性和有效性。导电材料及外源电刺激信号被证实对干细胞的增殖及分化行为具有积极的影响。本项目中，我们创新性地研究了三维导电支架介导的外源电信号对NSCs定向分化的作用。制备了基于导电聚合物聚3，4-乙撑二氧噻吩（PEDOT）的新型三维导电支架，并设计开发了基于三维导电支架的NSCs体外电刺激装置。蛋白和基因结果表明，合适的外源电信号参数可介导三维导电支架促进NSCs的增殖及干性维持。更重要的是，外源电信号协同导电支架增强了NSCs向神经元的分化，在该过程中细胞表面电压门控离子通道特别是钙离子通道发挥了关键作用。通过本项目的研究，为实现NSCs定向分化提供了一种有效的方法和策略，对基于干细胞疗法的神经再生修复具有重要临床应用价值。