Modulating the Electrical and Mechanical Microenvironment to Guide Neuronal Stem Cell Differentiation.
Modulating the Electrical and Mechanical Microenvironment to Guide Neuronal Stem Cell Differentiation.
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DOI：
10.1002/advs.202002112
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
George PM
中科院分区：
文献类型：
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作者：
Oh B;Wu YW;Swaminathan V;Lam V;Ding J;George PM
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 培养技术所需的长时间的限制。在这里，提出了一种导电石墨烯支架（CGS），用于调节机械和电信号以促进人类 iPSC 衍生的神经元。与一些传统方案相比，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 衍生神经元的生成率提高了五倍（14 天），并且成熟细胞标记物和电生理特征有所增加。与其他培养条件一致，我们发现机械和电刺激的促神经原性作用分别依赖于 RhoA/ROCK 信号传导和新生纤毛神经营养因子 (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。诱导多能干细胞是用于理解发育和再生医学的令人兴奋的细胞。干细胞对其环境做出反应以执行其功能并成熟。新设计的导电支架能够塑造机械和电气环境。利用这种导电聚合物平台，可以鉴定干细胞的增强干细胞神经元成熟和重要途径。
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. Induced pluripotent stem cells are exciting cells for understanding development and in regenerative medicine. Stem cells respond to their environment to perform their functions and mature. A newly designed conductive scaffold is capable of shaping the mechanical and electrical environment. Utilizing this conductive polymer platform, enhanced stem cell neuronal maturation of the stem cells and important pathways can be identified.