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Modulating the Electrical and Mechanical Microenvironment to Guide Neuronal Stem Cell Differentiation
Advanced Science ( IF 15.1 ) Pub Date : 2021-02-18 , DOI: 10.1002/advs.202002112
Byeongtaek Oh, Yu‐Wei Wu, Vishal Swaminathan, Vivek Lam, Jun Ding, Paul M. George

The application of induced pluripotent stem cells (iPSCs) in disease modeling and regenerative medicine can be limited by the prolonged times required for functional human neuronal differentiation and traditional 2D culture techniques. Here, a conductive graphene scaffold (CGS) to modulate mechanical and electrical signals to promote human iPSC‐derived neurons is presented. The soft CGS with cortex‐like stiffness (≈3 kPa) and electrical stimulation (±800 mV/100 Hz for 1 h) incurs a fivefold improvement in the rate (14d) of generating iPSC‐derived neurons over some traditional protocols, with an increase in mature cellular markers and electrophysiological characteristics. Consistent with other culture conditions, it is found that the pro‐neurogenic effects of mechanical and electrical stimuli rely on RhoA/ROCK signaling and de novo ciliary neurotrophic factor (CNTF) production respectively. Thus, the CGS system creates a combined physical and continuously modifiable, electrical niche to efficiently and quickly generate iPSC‐derived neurons.

中文翻译:

调节机电微环境以指导神经元干细胞分化

诱导多能干细胞 (iPSC) 在疾病建模和再生医学中的应用可能会受到功能性人类神经元分化和传统 2D 培养技术所需时间延长的限制。在这里,提出了一种用于调节机械和电信号以促进人类 iPSC 衍生神经元的导电石墨烯支架 (CGS)。与某些传统方案相比,具有皮质样刚度 (≈3 kPa) 和电刺激 (±800 mV/100 Hz,持续 1 小时) 的软 CGS 使 iPSC 衍生神经元的生成速率 (14d) 提高了五倍,成熟细胞标志物和电生理特征的增加。与其他文化条件一致,发现机械和电刺激的促神经作用分别依赖于 RhoA/ROCK 信号和从头睫状神经营养因子 (CNTF) 的产生。因此,CGS 系统创建了一个组合的物理和连续可修改的电生态位,以高效快速地生成 iPSC 衍生的神经元。
更新日期:2021-04-08
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