Multiplexed analysis of neural cytokine signaling by a novel neural cell-cell interaction microchip.
Multiplexed analysis of neural cytokine signaling by a novel neural cell-cell interaction microchip.
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DOI：
10.1039/d0lc00401d
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发表时间：
2020-11-07
期刊：
影响因子：
6.1
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Abdullah MAA;Amini N;Yang L;Paluh JL;Wang J
多能神经干细胞作为神经退行性疾病中促进组织再生的细胞来源被广泛应用于临床前和临床试验。通常作为解离的细胞、聚集体或自组织的细胞团递送，尚不清楚NSC玫瑰花结形态或形成方法的破坏是否影响这些细胞的信号传导谱，这可能影响细胞疗法中结果的均匀性。在这里，我们生成了一个神经细胞-细胞相互作用微芯片（NCCIM）作为体外平台，同时跟踪一组信息丰富的细胞因子，并共同评估细胞形态和生物标志物表达与夹心ELISA平台的结合。我们应用多重原位标记技术（MIST）对EB衍生的神经球、单细胞解离的神经球和重组的玫瑰花结神经球的10种细胞因子（PDGF-AA、GDNF、BDNF、IGF-1、FGF-2、IL-6、BMP-4、CNTF、β-NGF、NT-3）在微芯片上进行了评价。在所评估的细胞因子中，EB衍生的神经球显著分泌PDGF-AA、GDNF和FGF-2，而在解离成单细胞时该特征暂时丧失，并且在重组的神经球中还分泌两种另外的细胞因子BDNF和β-NGF。这项关于NSC细胞的研究证明了NCCIM作为高通量和受控微环境中细胞因子信号传导的敏感多重检测器的发展、多功能性和实用性。NCCIM有望提供重要的新信息，以完善治疗中的细胞来源选择，并支持开发信息丰富的2D或3D体外模型，包括神经变性或神经可塑性领域。神经细胞-细胞相互作用微芯片评估神经干细胞释放的10种细胞因子及其形态学和生物标志物表达。
Multipotent neural stem cells (NSCs) are widely applied in pre-clinical and clinical trials as a cell source to promote tissue regeneration in neurodegenerative diseases. Frequently delivered as dissociated cells, aggregates or self-organized rosettes, it is unknown whether disruption of the NSC rosette morphology or method of formation affect signaling profiles of these cells that may impact uniformity of outcomes in cell therapies. Here we generate a neural cell-cell interaction microchip (NCCIM) as an in vitro platform to simultaneously track an informed panel of cytokines and co-evaluate cell morphology and biomarker expression coupled to a sandwich ELISA platform. We apply multiplex in situ tagging technology (MIST) to evaluate ten cytokines (PDGF-AA, GDNF, BDNF, IGF-1, FGF-2, IL-6, BMP-4, CNTF, β-NGF, NT-3) on microchips for EB-derived rosettes, single cell dissociated rosettes and reformed rosette neurospheres. Of the cytokines evaluated, EB-derived rosettes secrete PDGF-AA, GDNF and FGF-2 prominently, whereas this profile is temporarily lost upon dissociation to single cells and in reformed neurospheres two additional cytokines, BDNF and β-NGF, are also secreted. This study on NSC rosettes demonstrates the development, versatility and utility of the NCCIM as a sensitive multiplex detector of cytokine signaling in a high throughput and controlled microenvironment. The NCCIM is expected to provide important new information to refine cell source choices in therapies as well as to support development of informative 2D or 3D in vitro models including areas of neurodegeneration or neuroplasticity. A neural cell-cell interaction microchip evaluates 10 cytokines released by neural stem cells and their morphology and biomarker expression.
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影响因子：
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作者：
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通讯作者：
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