旁分泌信号
细胞生物学
微尺度化学
多细胞生物
血管生成
电池类型
信号
生物
微流控
间质细胞
细胞
细胞信号
化学
纳米技术
信号转导
材料科学
受体
癌症研究
遗传学
数学教育
数学
作者
Jiaquan Yu,Erwin Berthier,Alexandria Craig,Theodorus E. de Groot,Sidney Sparks,Patrick Ingram,David F. Jarrard,Wei Huang,David J. Beebe,Ashleigh B. Theberge
标识
DOI:10.1038/s41551-019-0421-4
摘要
The study of intercellular signalling networks requires organotypic microscale systems that facilitate the culture, conditioning and manipulation of cells. Here, we describe a reconfigurable microfluidic cell-culture system that facilitates the assembly of three-dimensional tissue models by stacking layers that contain preconditioned microenvironments. By using principles of open and suspended microfluidics, the Stacks system is easily assembled or disassembled to provide spatial and temporal manoeuvrability in two-dimensional and three-dimensional assays of multiple cell types, enabling the modelling of sequential paracrine-signalling events, such as tumour-cell-mediated differentiation of macrophages and macrophage-facilitated angiogenesis. We used Stacks to recapitulate the in vivo observation that different prostate cancer tissues polarize macrophages with distinct gene-expression profiles of pro-inflammatory and anti-inflammatory cytokines. Stacks also enabled us to show that these two types of macrophages signal distinctly to endothelial cells, leading to blood vessels with different morphologies. Our proof-of-concept experiments exemplify how Stacks can efficiently model multicellular interactions and highlight the importance of spatiotemporal specificity in intercellular signalling. A reconfigurable microfluidic cell-culture system that facilitates the assembly of 3D tissue models by stacking layers containing preconditioned microenvironments enables the modelling of the spatiotemporal dynamics of paracrine signalling.
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