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Nat Methods. 2015 Dec;12(12):1197-204. doi: 10.1038/nmeth.3619. Epub 2015 Oct 19.

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

Author information

1
Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
2
Department of Biomedical Engineering, Rowan University, Glassboro, New Jersey, USA.
3
McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA.
4
Institute of Bioinformatics, International Technology Park, Bangalore, India.
5
High-Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
6
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
7
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
8
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
9
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
10
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

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.

PMID:
26480475
PMCID:
PMC4666781
DOI:
10.1038/nmeth.3619
[Indexed for MEDLINE]
Free PMC Article

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