title: Tissue matrix arrays for high-throughput screening and systems analysis of cell function.
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.
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.|Department of Biomedical Engineering, Rowan University, Glassboro, New Jersey, USA.
authors.forename: Vince Z
authors.initials: VZ
authors.lastname: Beachley
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Wolf
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: Sadtler
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA.|Institute of Bioinformatics, International Technology Park, Bangalore, India.
authors.forename: Srikanth S
authors.initials: SS
authors.lastname: Manda
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Jacobs
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Blatchley
authors.affiliation: High-Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Joel S
authors.identifier: http://orcid.org/0000-0002-6020-4625
authors.initials: JS
authors.lastname: Bader
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA.|Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Akhilesh
authors.identifier: http://orcid.org/0000-0001-9943-6127
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Drew
authors.initials: D
authors.lastname: Pardoll
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000502:physiology; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008855:Microscopy, Electron, Scanning; D009928:Organ Specificity; D020543:Proteome / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D013234:Stem Cells / Q000378:metabolism / Q000648:ultrastructure; D013552:Swine
chemical_list: D020543:Proteome