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基于患者来源的结直肠癌细胞类器官的药物筛选。

Drug screening by uniform patient derived colorectal cancer hydro-organoids.

机构信息

School of Mechanical Engineering, Korea University, Seoul, South Korea.

Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Open NBI Convergence Technology Laboratory, Avison Biomedical Research Center, Yonsei University College of Medicine, Seoul, South Korea.

出版信息

Biomaterials. 2021 Sep;276:121004. doi: 10.1016/j.biomaterials.2021.121004. Epub 2021 Jul 7.

DOI:10.1016/j.biomaterials.2021.121004
PMID:34273688
Abstract

As the importance of organoids increases, the need to develop organoid culture systems suitable for basic biological and clinical applications is being emphasized. However, there is still an unmet need to produce functionally complex and scalable uniform organoids. Here, we demonstrate a scalable organoid production platform with 8 well strips and a total of 8 × 9 microwells per strip using organoids derived from colorectal cancer tissue. The new culture platform is a format in which single cells are self-organized into organoids in culture medium supplemented with 2% Matrigel. It is functionally compatible with existing 96 well plates and Matrigel based conventional organoid culture methods. The consistency, uniformity and reproducibility of organoid produced on the new platform have been significantly improved compared to those of conventional plates. Importantly, Hydro-organoids are functionally identical to conventional Matrigel organoids, but show better consistency in drug screening. Our results show the possibility that Hydro-organoids can be used in high-throughput assays and incorporated into drug screening models to predict clinical outcomes.

摘要

随着类器官的重要性不断增加,开发适合基础生物学和临床应用的类器官培养系统的需求也越来越受到重视。然而,仍然需要生产具有功能复杂性和可扩展性的均匀类器官。在这里,我们展示了一种使用源自结直肠癌组织的类器官的 8 孔条和每条 8×9 微井的可扩展类器官生产平台。新的培养平台是一种在添加 2% Matrigel 的培养基中单细胞自组织成类器官的格式。它与现有的 96 孔板和基于 Matrigel 的传统类器官培养方法在功能上兼容。与传统平板相比,新平台上生成的类器官的一致性、均匀性和可重复性得到了显著提高。重要的是,Hydro-organoids 在功能上与传统的 Matrigel 类器官相同,但在药物筛选中表现出更好的一致性。我们的结果表明,Hydro-organoids 可用于高通量测定,并纳入药物筛选模型以预测临床结果。

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