面向临床前研究的三维类器官技术进展:面向体外人体模型

Yingjuan Liu, Honglin Xu, S. Abraham, X. Wang, B. Keavney
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引用次数: 1

摘要

刘颖娟*,徐宏林,Sabu Abraham,王鑫,Bernard D. Keavney*英国曼彻斯特大学生物医学与健康学院心血管科学部,M13 9PT,英国。*通讯:yingjuan.liu@manchester.ac.uk (Yingjuan Liu);bernard.keavney@manchester.ac.uk (Bernard D. Keavney)收稿日期:2022年11月1日接收日期:2022年11月24日发布日期:2022年12月21日摘要:目前,随着对新的治疗策略的需求增加,临床前药物测试或筛选平台近年来迅速发展。与传统的二维细胞培养相比,有或无支架的三维类器官或球体改善了体外培养的微环境,推进了体外生物学观察,使药物在人体类组织环境中的反应机理研究成为可能。3D类器官和球体的制作很简单,尺寸和形状也相对统一。这有助于促进高通量筛选要求。球体和类器官已被应用于抗癌药物测试、毒性评估以及各种器官系统的机制研究,包括肠、肝、胰腺、脑和心脏。在球体和类器官的三维培养中,由游离的肿瘤组织或癌细胞系形成的“肿瘤球体”成分相对简单,通常用于抗癌药物筛选。从hiPSCs/hESCs分化出来的“健康类器官”在细胞组成、分布、结构和功能上更复杂,与体内器官具有更高的相似性,并已在毒性测试、个性化药物以及治疗和机制研究中得到应用。在大多数情况下,多细胞3D类器官在体外对刺激或化学物质的反应更有抵抗力和稳定性,这表明更准确的体内反应建模。在此,我们综述了人类来源的类器官/球体系统及其在临床前研究中的应用的最新进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models
Review Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models Yingjuan Liu *, Honglin Xu, Sabu Abraham, Xin Wang, and Bernard D. Keavney* Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT, UK. * Correspondence: yingjuan.liu@manchester.ac.uk (Yingjuan Liu); bernard.keavney@manchester.ac.uk (Bernard D. Keavney)     Received: 1 November 2022 Accepted: 24 November 2022 Published: 21 December 2022   Abstract: Currently, with an increased requirement for new therapeutic strategies, preclinical drug testing or screening platforms have rapidly evolved in recent years. In comparison to traditional 2D cell cultures, 3D organoids or spheroids with or without scaffolds improve the microenvironment of in vitro cultures, advancing the in vitro biological observation and enabling mechanistic studies of drug reactions in the human tissue-like environment. 3D organoids and spheroids are straightforward to produce, and relatively uniform in size and shape. This helps to facilitate high throughput screening requirements. Spheroids and organoids have been applied in anti-cancer drug testing, toxicity evaluations, as well as mechanism studies for variable organ systems, including the intestine, liver, pancreas, brain, and heart. Among 3D cultures of spheroids and organoids, ‘tumour spheroids’ formed by dissociated tumour tissues or cancer cell lines are relatively simple in composition and commonly applied to anticancer drug screening. The ‘healthy organoids’ differentiated from hiPSCs/hESCs are more complex in cell composition, distribution, structure and function with higher similarity to in vivo organs, and have found applications in toxicity tests, personalised medicine, and therapeutic and mechanistic studies. In most cases, the multicellular 3D organoids are more resistant and stable in reaction to stimulations or chemicals in vitro , suggesting more accurate modelling of in vivo responses. Here, we review recent progress in human-origin organoid/spheroid systems and their applications in preclinical studies.
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