A multiscale fluidic device for the study of dendrite-mediated cell to cell communication.

A multiscale fluidic device for the study of dendrite-mediated cell to cell communication.
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DOI:
10.1007/s10544-017-0212-1
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发表时间:
2017-08-08
影响因子:
2.8
通讯作者:
Vazquez M
Vazquez M
中科院分区:
工程技术3区
文献类型:
--
作者:
McCutcheon S;Majeska R;Schaffler M;Vazquez M

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许多类型的细胞通过树突状延伸通过一组多层的几何和化学线索进行交流。直到最近,以空间和时间可控的方式模拟树突表达细胞(如骨细胞和运动神经元)的体内区室化细胞环境受到亚微米尺度的体外装置制造的挑战的限制。利用当前制造技术的改进分辨率,我们设计了一种多尺度装置,即宏微纳系统,或Mμn,由两个不同的细胞接种和询问室组成,由纳米通道阵列隔开。该阵列能够使树突向内生长,同时提供用于流体隔离和/或细胞群体之间的暂时介导的可扩散信号传导的机制。Mμn系统的建模预测了分离可扩散信号的能力,即ATP。经验扩散研究验证了计算模型。此外,在骨细胞和运动神经元的装置内,对细胞活力、树突与纳米阵列的相互作用以及细胞对热休克的嘌呤能反应进行了实验性评价。我们的研究结果描述了一种新的体外系统,其中树突表达细胞类型可以在模拟体内条件的纳米环境中进行研究。特别是,Mμn系统能够实时观察不同但流体耦合区域中细胞群之间的细胞间通讯。
Many cell types communicate by means of dendritic extensions via a multi-tiered set of geometric and chemical cues. Until recently, mimicking the compartmentalized in vivo cellular environment of dendrite-expressing cells such as osteocytes and motor neurons in a spatially and temporally controllable manner was limited by the challenges of in vitro device fabrication at submicron scales. Utilizing the improved resolution of current fabrication technology, we have designed a multiscale device, the Macro-micro-nano system, or Mμn, composed of two distinct cell-seeding and interrogation compartments separated by a nanochannel array. The array enables dendrite ingrowth, while providing a mechanism for fluidic sequestration and/or temporally-mediated diffusible signaling between cell populations. Modeling of the Mμn system predicted the ability to isolate diffusible signals, namely ATP. Empirical diffusion studies verified computational modeling. In addition, cell viability, dendrite interaction with the nanoarray, and cellular purinergic response to heat shock were experimentally evaluated within the device for both osteocytes and motor neurons. Our results describe a novel in vitro system in which dendrite-expressing cell types can be studied within nano-environments that mimic in vivo conditions. In particular, the Mμn system enables real-time observation of cell to cell communication between cell populations in distinct, but fluidically coupled regions.
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