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High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays


Brandenberg, Nathalie; Hoehnel, Sylke; Kuttler, Fabien; Homicsko, Krisztian; Ceroni, Camilla; Ringel, Till; Gjorevski, Nikolce; Schwank, Gerald; Coukos, George; Turcatti, Gerardo; Lutolf, Matthias P (2020). High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays. Nature Biomedical Engineering, 4(9):863-874.

Abstract

Stem-cell-derived epithelial organoids are routinely used for the biological and biomedical modelling of tissues. However, the complexity, lack of standardization and quality control of stem cell culture in solid extracellular matrices hampers the routine use of the organoids at the industrial scale. Here, we report the fabrication of microengineered cell culture devices and scalable and automated methods for suspension culture and real-time analysis of thousands of individual gastrointestinal organoids trapped in microcavity arrays within a polymer-hydrogel substrate. The absence of a solid matrix substantially reduces organoid heterogeneity, which we show for mouse and human gastrointestinal organoids. We use the devices to screen for anticancer drug candidates with patient-derived colorectal cancer organoids, and apply high-content image-based phenotypic analyses to reveal insights into mechanisms of drug action. The scalable organoid-culture technology should facilitate the use of organoids in drug development and diagnostics.

Abstract

Stem-cell-derived epithelial organoids are routinely used for the biological and biomedical modelling of tissues. However, the complexity, lack of standardization and quality control of stem cell culture in solid extracellular matrices hampers the routine use of the organoids at the industrial scale. Here, we report the fabrication of microengineered cell culture devices and scalable and automated methods for suspension culture and real-time analysis of thousands of individual gastrointestinal organoids trapped in microcavity arrays within a polymer-hydrogel substrate. The absence of a solid matrix substantially reduces organoid heterogeneity, which we show for mouse and human gastrointestinal organoids. We use the devices to screen for anticancer drug candidates with patient-derived colorectal cancer organoids, and apply high-content image-based phenotypic analyses to reveal insights into mechanisms of drug action. The scalable organoid-culture technology should facilitate the use of organoids in drug development and diagnostics.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Biotechnology
Physical Sciences > Bioengineering
Health Sciences > Medicine (miscellaneous)
Physical Sciences > Biomedical Engineering
Physical Sciences > Computer Science Applications
Language:English
Date:September 2020
Deposited On:18 Jan 2021 12:22
Last Modified:19 Jan 2021 21:01
Publisher:Springer
ISSN:2157-846X
OA Status:Closed
Publisher DOI:https://doi.org/10.1038/s41551-020-0565-2
PubMed ID:32514094

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