Tissue matrix arrays for high-throughput screening and systems analysis of cell function

被引:139
作者
Beachley, Vince Z. [1 ,2 ,3 ]
Wolf, Matthew T. [1 ,2 ]
Sadtler, Kaitlyn [1 ,2 ]
Manda, Srikanth S. [4 ,5 ]
Jacobs, Heather [1 ,2 ]
Blatchley, Michael R. [1 ,2 ]
Bader, Joel S. [2 ,6 ]
Pandey, Akhilesh [4 ,7 ,8 ,9 ]
Pardoll, Drew [10 ]
Elisseeff, Jennifer H. [1 ,2 ]
机构
[1] Johns Hopkins Univ, Wilmer Eye Inst, Translat Tissue Engn Ctr, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA
[3] Rowan Univ, Dept Biomed Engn, Glassboro, NJ USA
[4] McKusick Nathans Inst Genet Med, Baltimore, MD USA
[5] Inst Bioinformat, Bangalore, Karnataka, India
[6] Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD USA
[7] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
[8] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[9] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[10] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA
关键词
EXTRACELLULAR-MATRIX; NICHE MICROARRAYS; BIOMATERIALS; CARCINOMA; PLATFORM; GRAFT;
D O I
10.1038/nmeth.3619
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
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 spotted tissue extracellular matrix (ECM) particles as two-dimensional (2D) arrays or incorporated them with cells to generate three-dimensional (3D) cell-matrix microtissue arrays. We then investigated the responses of human stem, cancer and immune cells to tissue ECM arrays originating from 11 different tissues. We validated the 2D and 3D arrays as representative of the in vivo microenvironment by means of quantitative analysis of tissue-specific cellular responses, including matrix production, adhesion and proliferation, and morphological changes after 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 further understanding of regeneration and disease mechanisms.
引用
收藏
页码:1197 / +
页数:14
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