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Multi-compartment tumor organoids
Materials Today ( IF 21.1 ) Pub Date : 2022-10-29 , DOI: 10.1016/j.mattod.2022.07.006
Meng-Horng Lee , Gabriella C. Russo , Yohan Suryo Rahmanto , Wenxuan Du , Ashleigh J. Crawford , Pei-Hsun Wu , Daniele Gilkes , Ashley Kiemen , Tsutomu Miyamoto , Yu Yu , Mehran Habibi , Ie-Ming Shih , Tian-Li Wang , Denis Wirtz

Organoid cultures are widely used for tumor modeling because they preserve many phenotypic features of cancer cells in vivo. However, current organoids present issues of consistency, efficiency, mimicry, and cell-seeding control. More importantly, they can only contain only one extracellular matrix (ECM) compartment at a time, while solid tumors feature two main ECM compartments: the basement membrane and the stromal matrix. Here, we develop, test, and validate a high-throughput oil-in-water droplet microtechnology to generate highly uniform, small-volume, multi-compartment organoids. Each organoid culture features microenvironmental architectures that mimic both the basement membrane and stromal barriers. This matrix architecture, which allows us to simultaneously take into account and assess the proliferative and invasive properties of cancer cells in a single platform, has profound effect on observed drug responsiveness and tumor progression that correlate well with in vivo and clinical outcomes. Our method was tested on multiple types of cells including primary breast and ovarian cancer cells and immortalized cell lines, and we determined our platform is suitable even for cancer cells of poor standard organoid-forming ability such as primary patient samples. These new organoids also allow for direct orthotopic mouse implantation of cancer cells with unprecedented success.



中文翻译:

多室肿瘤类器官

类器官培养物广泛用于肿瘤建模,因为它们在体内保留了癌细胞的许多表型特征. 然而,目前的类器官存在一致性、效率、拟态和细胞接种控制等问题。更重要的是,它们一次只能包含一个细胞外基质 (ECM) 隔室,而实体瘤具有两个主要的 ECM 隔室:基底膜和基质。在这里,我们开发、测试和验证了一种高通量的水包油微技术,以生成高度均匀、小体积、多隔室的类器官。每种类器官培养物都具有模拟基底膜和基质屏障的微环境结构。这种矩阵架构使我们能够在单一平台中同时考虑和评估癌细胞的增殖和侵袭特性,体内和临床结果。我们的方法在多种类型的细胞上进行了测试,包括原发性乳腺癌和卵巢癌细胞以及永生化细胞系,我们确定我们的平台甚至适用于标准类器官形成能力较差的癌细胞,例如原发性患者样本。这些新的类器官还允许直接原位小鼠植入癌细胞,取得了前所未有的成功。

更新日期:2022-10-29
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