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High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays.
Nature Biomedical Engineering ( IF 28.1 ) Pub Date : 2020-06-08 , DOI: 10.1038/s41551-020-0565-2
Nathalie Brandenberg 1, 2 , Sylke Hoehnel 1, 2 , Fabien Kuttler 3 , Krisztian Homicsko 4 , Camilla Ceroni 1, 2 , Till Ringel 5 , Nikolce Gjorevski 1, 6 , Gerald Schwank 5 , George Coukos 4 , Gerardo Turcatti 3 , Matthias P Lutolf 1, 7
Affiliation  

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.



中文翻译:

通过微腔阵列中的干细胞聚集进行高通量自动化类器官培养。

干细胞衍生的上皮类器官通常用于组织的生物学和生物医学建模。然而,固体细胞外基质中干细胞培养的复杂性,缺乏标准化和质量控制,妨碍了类器官在工业规模上的常规使用。在这里,我们报告微工程细胞培养设备的制造以及悬浮培养的实时和可扩展的自动化方法,以及对聚合物水凝胶基质内微腔阵列中捕获的数千种胃肠道类器官的实时分析。固体基质的缺乏大大降低了类器官的异质性,这在小鼠和人类胃肠类器官中表现出来。我们使用这些设备来筛选具有患者源性大肠癌类器官的抗癌药物,并应用基于图像的高含量表型分析来揭示对药物作用机制的见解。可扩展的类器官培养技术应有助于在药物开发和诊断中使用类器官。

更新日期:2020-06-08
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