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类器官在泌尿系统癌症研究中的潜力。

The potential of organoids in urological cancer research.

机构信息

Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.

Urology Department, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

出版信息

Nat Rev Urol. 2017 Jul;14(7):401-414. doi: 10.1038/nrurol.2017.65. Epub 2017 May 23.

Abstract

Technical advances in the development of organoid systems enable cell lines, primary adult cells, or stem or progenitor cells to develop into diverse, multicellular entities, which can self-renew, self-organize, and differentiate. These 3D organoid cultures have proven to be of value in increasing our understanding of the biology of disease and offer the potential of regenerative and genetic therapies. The successful application of 3D organoids derived from adult tissue into urological cancer research can further our understanding of these diseases and could also provide preclinical cancer models to realize the precision medicine paradigm by therapeutic screening of individual patient samples ex vivo. Kidney organoids derived from induced pluripotent stem cells provide personalized biomarkers, which can be correlated with genetic and clinical information. Organoid models can also improve our comprehension of aspects of particular diseases; for example, in prostate cancer, 3D organoids can aid in the identification of tumour-initiating cells from an epithelial cell lineage. Furthermore, kidney organoid differentiation from human pluripotent stem cells enables gene editing to model disease in kidney tubular epithelial cells. State-of-the-art human organoid cultures have potential as tools in basic and clinical research in renal, bladder, and prostatic diseases.

摘要

器官发生系统的技术进步使细胞系、成人原代细胞或干细胞或祖细胞能够发育成多样化的多细胞实体,这些实体能够自我更新、自我组织和分化。这些 3D 类器官培养物已被证明在提高我们对疾病生物学的认识方面具有价值,并为再生和基因治疗提供了潜力。成功地将源自成人组织的 3D 类器官应用于尿路上皮癌研究,可以进一步加深我们对这些疾病的认识,并且还可以提供临床前癌症模型,通过对个体患者样本进行离体治疗筛选来实现精准医学范例。诱导多能干细胞衍生的肾类器官提供了个性化的生物标志物,可以与遗传和临床信息相关联。类器官模型还可以帮助我们更好地理解某些疾病的方面;例如,在前列腺癌中,3D 类器官可以帮助从上皮细胞谱系中鉴定肿瘤起始细胞。此外,人多能干细胞衍生的肾类器官分化使基因编辑能够模拟肾小管上皮细胞中的疾病。最先进的人类类器官培养物有可能成为肾脏、膀胱和前列腺疾病基础和临床研究的工具。

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本文引用的文献

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Cancer Statistics, 2017.《2017 年癌症统计》
CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
4
Generation of kidney organoids from human pluripotent stem cells.从人类多能干细胞生成肾类器官。
Nat Protoc. 2016 Sep;11(9):1681-92. doi: 10.1038/nprot.2016.098. Epub 2016 Aug 18.

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