Probing the role of multicellular organization in three-dimensional microenvironments

Successful application of living cells in regenerative medicine requires an understanding of how tissue structure relates to organ function. There is growing evidence that presentation of extracellular cues in a three-dimensional (3D) context can fundamentally alter cellular responses. Thus, microen...

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Veröffentlicht in:Nature methods 2006-05, Vol.3 (5), p.369-375
Hauptverfasser: Bhatia, Sangeeta N, Albrecht, Dirk R, Underhill, Gregory H, Wassermann, Travis B, Sah, Robert L
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container_issue 5
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container_title Nature methods
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creator Bhatia, Sangeeta N
Albrecht, Dirk R
Underhill, Gregory H
Wassermann, Travis B
Sah, Robert L
description Successful application of living cells in regenerative medicine requires an understanding of how tissue structure relates to organ function. There is growing evidence that presentation of extracellular cues in a three-dimensional (3D) context can fundamentally alter cellular responses. Thus, microenvironment studies that previously were limited to adherent two-dimensional (2D) cultures may not be appropriate for many cell types. Here we present a method for the rapid formation of reproducible, high-resolution 3D cellular structures within a photopolymerizable hydrogel using dielectrophoretic forces. We demonstrate the parallel formation of >20,000 cell clusters of precise size and shape within a thin 2-cm 2 hydrogel and the maintenance of high cell viability and differentiated cell markers over 2 weeks. By modulating cell-cell interactions in 3D clusters, we present the first evidence that microscale tissue organization regulates bovine articular chondrocyte biosynthesis. This platform permits investigation of tissue architecture in other multicellular processes, from embryogenesis to regeneration to tumorigenesis.
doi_str_mv 10.1038/nmeth873
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subjects Animals
Bioinformatics
Biological Microscopy
Biological Techniques
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biosensing Techniques - methods
Biosynthesis
Cartilage cells
Cartilage, Articular - cytology
Cartilage, Articular - pathology
Cattle
Cell culture
Cell Culture Techniques - methods
Cell Differentiation
Cell interaction
Cell Survival
Cellular biology
Chondrocytes - cytology
Chondrocytes - pathology
Dielectrics
DNA probes
Electromagnetic Fields
Embryonic Development - physiology
Embryonic growth stage
Genetic aspects
Hydrogels - chemistry
Imaging, Three-Dimensional
Life Sciences
Methods
Microenvironments
Neoplasms - pathology
Physiological aspects
Proteomics
Regeneration - physiology
Time Factors
Tissue Engineering
Tissues
Tumor Cells, Cultured - pathology
title Probing the role of multicellular organization in three-dimensional microenvironments
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