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从诱导多能干细胞(iPSCs)中生成肝类器官:肝癌研究中类器官生成的另一种来源。

Developing liver organoids from induced pluripotent stem cells (iPSCs): An alternative source of organoid generation for liver cancer research.

机构信息

Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW 2145, Australia.

Storr Liver Centre, Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, NSW 2145, Australia.

出版信息

Cancer Lett. 2021 Jun 28;508:13-17. doi: 10.1016/j.canlet.2021.03.017. Epub 2021 Mar 23.

Abstract

Primary liver cancer (PLC) represents a significant proportion of all human cancers and constitutes a substantial health and economic burden to society. Traditional therapeutic approaches such as surgical resection and chemotherapy often fail due to tumour relapse or innate tumour chemoresistance. There is a dearth of efficient treatments for PLC in part due to the poor capacity of current laboratory models to reflect critical features of the native tumour in vivo. The increasing incorporation of organoid systems has led to a resurgence of interest in liver cancer research. Organoid systems show promise as the gold standard for recapitulating tumours in vitro. Further, developments in culturing techniques will improve the various shortcomings of the current systems. Induced pluripotent stem cell (iPSC)-derived liver organoids are a promising alternative to the conventional liver organoid model as it circumvents the need to rely on primary resections which are often scarce. In this concise review, we will discuss novel techniques for organoid culture with a focus on organoid co-cultures and their advantages over traditional organoid systems. A detailed technical protocol for the generation of iPSC-derived liver organoids is provided as an appendix.

摘要

原发性肝癌(PLC)在所有人类癌症中占很大比例,给社会带来了巨大的健康和经济负担。由于肿瘤复发或固有肿瘤化疗耐药性,传统的治疗方法,如手术切除和化疗,往往失败。部分原因是由于目前的实验室模型不能很好地反映体内肿瘤的关键特征,导致 PLC 缺乏有效的治疗方法。类器官系统的不断引入重新引起了人们对肝癌研究的兴趣。类器官系统有望成为体外重现肿瘤的金标准。此外,培养技术的发展将改善当前系统的各种缺点。诱导多能干细胞(iPSC)衍生的肝类器官是传统肝类器官模型的一种有前途的替代方法,因为它避免了对通常稀缺的原发性切除的依赖。在这篇简明的综述中,我们将讨论类器官培养的新技术,重点是类器官共培养及其相对于传统类器官系统的优势。提供了 iPSC 衍生的肝类器官生成的详细技术方案作为附录。

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