Department of Medical Sciences, Graduate School of Medicine, Korea University, Seoul, Korea.
Department of Advanced Material Science and Engineering, College of Engineering, Kangwon National University, Chuncheon, 25561, Korea.
Sci Rep. 2019 Apr 9;9(1):5827. doi: 10.1038/s41598-019-42320-9.
Electrical stimulation of cells and tissues for therapeutic benefit is a well-established method. Although animal studies can emulate the complexity of an organism's physiology, lab-on-a-chip platforms provide a suitable primary model for follow-up animal studies. Thus, inexpensive and easy-to-use platforms for in vitro human cell studies are required. In the present study, we designed a micro-electrical impulse (micro-EI)-on-a-chip (micro-EI-chip), which can precisely control electron density and adjust the frequency based on a micro-EI. The micro-EI-chip can stimulate cells at various micro-EI densities (0-500 mV/mm) and frequencies (0-300 Hz), which enables multiple co-culture of different cell types with or without electrical stimulation. As a proof-of-concept study, a model involving degenerative inflamed human annulus fibrosus (hAF) cells was established in vitro and the effects of micro-EI on inflamed hAF cells were evaluated using the micro-EI-chip. Stimulation of the cells (150 mV/mm at 200 Hz) inhibited the secretion of inflammatory cytokines and downregulated the activities of extracellular matrix-modifying enzymes and matrix metalloproteinase-1. These results show that micro-EI stimulation could affect degenerative diseases based on inflammation, implicating the micro-EI-chip as being useful for basic research of electroceuticals.
电刺激细胞和组织以达到治疗效果是一种成熟的方法。尽管动物研究可以模拟生物体生理学的复杂性，但芯片上实验室平台为后续的动物研究提供了合适的初步模型。因此，需要廉价且易于使用的体外人类细胞研究平台。在本研究中，我们设计了一种微电脉冲（micro-EI）-on-a-chip（micro-EI-chip），它可以根据 micro-EI 精确控制电子密度并调整频率。micro-EI-chip 可以在各种 micro-EI 密度（0-500 mV/mm）和频率（0-300 Hz）下刺激细胞，从而可以进行不同细胞类型的多种共培养，无论是否进行电刺激。作为概念验证研究，在体外建立了涉及退行性炎症人纤维环（hAF）细胞的模型，并使用 micro-EI-chip 评估了 micro-EI 对炎症 hAF 细胞的影响。细胞刺激（150 mV/mm，200 Hz）抑制了炎症细胞因子的分泌，并下调了细胞外基质修饰酶和基质金属蛋白酶-1 的活性。这些结果表明，micro-EI 刺激可能会影响基于炎症的退行性疾病，这表明 micro-EI-chip 可用于电疗的基础研究。
