Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling
Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling
复制标题
纳米级地形的电刺激通过增强自噬信号传导促进神经干细胞的神经发生。
DOI：
10.1016/j.biomaterials.2020.120585
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发表时间：
2021-01-01
期刊：
影响因子：
14
通讯作者：
Chiu, Kin
中科院分区：
文献类型：
--
作者：
He, Liumin;Sun, Zhongqing;Chiu, Kin
神经干细胞移植于中枢神经系统损伤部位，使神经再生成为可能。神经干细胞移植后的长期存活和低增殖、分化、迁移率一直是神经干细胞应用中最具挑战性的方面。设计了一种新的多通道电刺激（ES）装置，用于促进神经干细胞（NSCs）分化为成熟神经元。与对照组相比，ES在纳米形貌增强成熟神经元标记物的表达，神经突起的生长，BDNF的浓度和电生理活性。RNA测序分析证实ES通过增强自噬信号促进神经干细胞分化。新的证据表明，不足或过度的自噬有助于神经突变性。过量的ES电流能增强神经元的自噬，神经元细胞的存活率降低，轴突生长和电生理活性降低。良好控制的自噬不仅可以防止神经退行性变，还可以调节神经发生。目前的NSC处理方案通过结合适当的ES条件以及细胞培养系统中自噬水平的平衡来有效地增强NSC的分化、成熟和存活。经预处理后的神经干细胞移植于受损部位的成功率将显著提高。
Neural stem cells (NSCs) transplantation at the injury site of central nerve system (CNS) makes it possible for neuroregeneration. Long-term cell survival and low proliferation, differentiation, and migration rates of NSCs graft have been the most challenging aspect on NSCs application. New multichannel electrical stimulation (ES) device was designed to enhance neural stem cells (NSCs) differentiation into mature neurons. Compared to controls, ES at nanoscale topography enhanced the expression of mature neuronal marker, growth of the neurites, concentration of BDNF and electrophysiological activity. RNA sequencing analysis validated that ES promoted NSC-derived neuronal differentiation through enhancing autophagy signaling. Emerging evidences showed that insufficient or excessive autophagy contributes to neurite degeneration. Excessive ES current were able to enhance neuronal autophagy, the neuronal cells showed poor viability, reduced neurite outgrowth and electrophysiological activity. Well-controlled autophagy not only protects against neurodegeneration, but also regulates neurogenesis. Current NSC treatment protocol efficiently enhanced NSC differentiation, maturation and survival through combination of proper ES condition followed by balance of autophagy level in the cell culture system. The successful rate of such protreated NSC at injured CNS site should be significantly improved after transplantation.