Reconfigurable open microfluidics for studying the spatiotemporal dynamics of paracrine signalling.

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  • Additional Information
    • Source:
      Publisher: Springer Nature Country of Publication: England NLM ID: 101696896 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2157-846X (Electronic) Linking ISSN: 2157846X NLM ISO Abbreviation: Nat Biomed Eng Subsets: MEDLINE
    • Publication Information:
      Publication: London : Springer Nature
      Original Publication: [London] : Macmillan Publishers Limited, [2016]-
    • Subject Terms:
      Signal Transduction* ; Spatio-Temporal Analysis*; Cell Culture Techniques/*methods ; Microfluidic Analytical Techniques/*methods ; Microfluidics/*methods; Cytokines/metabolism ; Endothelial Cells ; Humans ; Macrophages ; Microfluidic Analytical Techniques/instrumentation ; Microfluidics/instrumentation ; Transcriptome ; Tumor Microenvironment
    • Abstract:
      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.
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    • Grant Information:
      K12 DK100022 United States DK NIDDK NIH HHS; P30 CA014520 United States CA NCI NIH HHS; R35 GM128648 United States GM NIGMS NIH HHS; T32 HL007899 United States HL NHLBI NIH HHS; R01 CA185251 United States CA NCI NIH HHS; R01 EB010039 United States EB NIBIB NIH HHS
    • Accession Number:
      0 (Cytokines)
    • Publication Date:
      Date Created: 20190821 Date Completed: 20200309 Latest Revision: 20201010
    • Publication Date:
      20231215
    • Accession Number:
      PMC7543914
    • Accession Number:
      10.1038/s41551-019-0421-4
    • Accession Number:
      31427781