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用于癌症和毒理学研究的人体类器官及辅助技术

Human Organoid and Supporting Technologies for Cancer and Toxicological Research.

作者信息

Sekine Keisuke

机构信息

Laboratory of Cancer Cell Systems, National Cancer Center Research Institute, Tokyo, Japan.

出版信息

Front Genet. 2021 Oct 22;12:759366. doi: 10.3389/fgene.2021.759366. eCollection 2021.

Abstract

Recent progress in the field of organoid-based cell culture systems has enabled the use of patient-derived cells in conditions that resemble those in cancer tissue, which are better than two-dimensional (2D) cultured cell lines. In particular, organoids allow human cancer cells to be handled in conditions that resemble those in cancer tissue, resulting in more efficient establishment of cells compared with 2D cultured cell lines, thus enabling the use of multiple patient-derived cells with cells from different genetic background, in keeping with the heterogeneity of the cells. One of the most valuable points of using organoids is that human cells from either healthy or cancerous tissue can be used. Using genome editing technology such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein, organoid genomes can be modified to, for example, cancer-prone genomes. The normal, cancer, or genome-modified organoids can be used to evaluate whether chemicals have genotoxic or non-genotoxic carcinogenic activity by evaluating the cancer incidence, cancer progression, and cancer metastasis. In this review, the organoid technology and the accompanying technologies were summarized and the advantages of organoid-based toxicology and its application to pancreatic cancer study were discussed.

摘要

基于类器官的细胞培养系统领域的最新进展,使得在类似于癌症组织的条件下使用患者来源的细胞成为可能,这比二维(2D)培养的细胞系更具优势。特别是,类器官允许在类似于癌症组织的条件下处理人类癌细胞,与二维培养的细胞系相比,能更高效地建立细胞系,从而能够将多个患者来源的细胞与具有不同遗传背景的细胞一起使用,这与细胞的异质性相符。使用类器官最有价值的一点在于,无论是健康组织还是癌组织的人类细胞都可以使用。利用诸如成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关蛋白等基因组编辑技术,类器官基因组可以被修饰,例如修饰成易于患癌的基因组。正常、癌症或基因组修饰的类器官可用于通过评估癌症发病率、癌症进展和癌症转移来评价化学物质是否具有基因毒性或非基因毒性致癌活性。在本综述中,总结了类器官技术及相关技术,并讨论了基于类器官的毒理学的优势及其在胰腺癌研究中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/123d/8569236/354f60f494ac/fgene-12-759366-g001.jpg

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