Tissue matrix arrays for high-throughput screening and systems analysis of cell function.
Tissue matrix arrays for high-throughput screening and systems analysis of cell function.
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DOI：
10.1038/nmeth.3619
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发表时间：
2015-12
期刊：
影响因子：
48
通讯作者：
Elisseeff JH
中科院分区：
文献类型：
--
作者：
Beachley VZ;Wolf MT;Sadtler K;Manda SS;Jacobs H;Blatchley MR;Bader JS;Pandey A;Pardoll D;Elisseeff JH
细胞和蛋白质阵列在生物反应的高通量评估中显示出显著的实用价值；然而，它们缺乏天然组织和器官的复杂性。在这里，我们描述了用于筛选生物输出和系统分析的组织细胞外基质(ECM)阵列。我们将经过处理的组织细胞外基质颗粒定位为二维阵列，或者将它们与细胞结合生成三维细胞基质微组织阵列。然后，我们研究了来自11个不同组织的组织ECM阵列对人类干细胞、癌症和免疫细胞的响应，并通过定量分析组织特异性细胞反应，包括基质产生、黏附和增殖以及培养后的形态变化，验证了2D和3D阵列是代表体内微环境的。生物产出与组织蛋白质组学相关，网络分析确定了几种与细胞功能有关的蛋白质。我们的方法能够对细胞外基质进行广泛的筛选，将组织特异性成分与生物活性联系起来，为生物材料研究和翻译提供新的资源。
Cell and protein arrays have demonstrated remarkable utility in the high-throughput evaluation of biological responses; however, they lack the complexity of native tissue and organs. Here, we describe tissue extracellular matrix (ECM) arrays for screening biological outputs and systems analysis. We spotted processed tissue ECM particles as two-dimensional arrays or incorporated them with cells to generate three-dimensional cell-matrix microtissue arrays. We then investigated the response of human stem, cancer, and immune cells to tissue ECM arrays originating from 11 different tissues, and validated the 2D and 3D arrays as representative of the in vivo microenvironment through quantitative analysis of tissue-specific cellular responses, including matrix production, adhesion and proliferation, and morphological changes following culture. The biological outputs correlated with tissue proteomics, and network analysis identified several proteins linked to cell function. Our methodology enables broad screening of ECMs to connect tissue-specific composition with biological activity, providing a new resource for biomaterials research and translation.