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Translational models of 3-D organoids and cancer stem cells in gastric cancer research
Stem Cell Research & Therapy ( IF 7.1 ) Pub Date : 2021-09-06 , DOI: 10.1186/s13287-021-02521-4
Kenly Wuputra , Chia-Chen Ku , Kohsuke Kato , Deng-Chyang Wu , Shigeo Saito , Kazunari K. Yokoyama

It is postulated as a general concept of cancer stem cells (CSCs) that they can produce cancer cells overtly and repopulate cancer progenitor cells indefinitely. The CSC niche is part of a specialized cancer microenvironment that is important to keep the phenotypes of CSCs. Stem cell- and induced pluripotent stem cell (iPSC)-derived organoids with genetic manipulation are beneficial to the investigation of the regulation of the microenvironment of CSCs. It would be useful to assess the efficiency of the cancer microenvironment on initiation and progression of cancers. To identify CSCs in cancer tissues, normal cell organoids and gastric cancer organoids from the cancerous areas, as well as iPSCs, were established several years ago. However, many questions remain about the extent to which these cultures recapitulate the development of the gastrointestinal tract and the mechanism of Helicobacter pylori-induced cancer progression. To clarify the fidelity of human organoid models, we have noted several key issues for the cultivation of, and differences between, normal and cancerous organoids. We developed precise culture conditions for gastric organoids in vitro to improve the accuracy of the generation of organoid models for therapeutic and medical applications. In addition, the current knowledge on gastrointestinal CSC research, including the topic of CSC markers, cancer cell reprogramming, and application to target cancer cell plasticity through niches, should be reinforced. We discuss the progression of cancers derived from human gastric organoids and the identification of CSCs.

中文翻译:

胃癌研究中 3-D 类器官和癌症干细胞的转化模型

它被假定为癌症干细胞 (CSC) 的一般概念,即它们可以公开产生癌细胞并无限期地重新填充癌症祖细胞。CSC 生态位是专门的癌症微环境的一部分,对于保持 CSC 的表型很重要。具有基因操作的干细胞和诱导多能干细胞 (iPSC) 衍生的类器官有利于研究 CSC 微环境的调节。评估癌症微环境对癌症发生和进展的效率将是有用的。为了识别癌组织中的 CSC,几年前建立了来自癌区的正常细胞类器官和胃癌类器官,以及 iPSC。然而,关于这些培养物在多大程度上概括了胃肠道的发展和幽门螺杆菌诱导的癌症进展的机制,许多问题仍然存在。为了阐明人体类器官模型的保真度,我们注意到了培养正常类器官和癌变类器官的几个关键问题以及它们之间的差异。我们在体外为胃类器官开发了精确的培养条件,以提高用于治疗和医学应用的类器官模型生成的准确性。此外,目前对胃肠 CSC 研究的知识,包括 CSC 标志物、癌细胞重编程以及通过生态位靶向癌细胞可塑性的应用等,都应该得到加强。我们讨论源自人类胃类器官的癌症的进展和 CSCs 的鉴定。
更新日期:2021-09-06
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