文章：

用微流控人体器官芯片模拟癌症

Modelling cancer in microfluidic human organs-on-chips

原文发布日期：2019-01-15

DOI: 10.1038/s41568-018-0104-6

类型: Review Article

开放获取: 否

英文摘要：

One of the problems that has slowed the development and approval of new anticancer therapies is the lack of preclinical models that can be used to identify key molecular, cellular and biophysical features of human cancer progression. This is because most in vitro cancer models fail to faithfully recapitulate the local tissue and organ microenvironment in which tumours form, which substantially contributes to the complex pathophysiology of the disease. More complex in vitro cancer models have been developed, including transwell cell cultures, spheroids and organoids grown within flexible extracellular matrix gels, which better mimic normal and cancerous tissue development than cells maintained on conventional 2D substrates. But these models still lack the tissue–tissue interfaces, organ-level structures, fluid flows and mechanical cues that cells experience within living organs, and furthermore, it is difficult to collect samples from the different tissue microcompartments. In this Review, we outline how recent developments in microfluidic cell culture technology have led to the generation of human organs-on-chips (also known as organ chips) that are now being used to model cancer cell behaviour within human-relevant tissue and organ microenvironments in vitro. Organ chips enable experimentalists to vary local cellular, molecular, chemical and biophysical parameters in a controlled manner, both individually and in precise combinations, while analysing how they contribute to human cancer formation and progression and responses to therapy. We also discuss the challenges that must be overcome to ensure that organ chip models meet the needs of cancer researchers, drug developers and clinicians interested in personalized medicine.

摘要翻译： 

阻碍抗癌新疗法研发和获批的问题之一，是缺乏能够识别人类癌症进展关键分子、细胞及生物物理学特征的临床前模型。这主要是因为大多数体外癌症模型无法真实再现肿瘤形成的局部组织与器官微环境，而这种微环境对疾病复杂病理生理机制的形成具有重要影响。目前虽已开发出更复杂的体外癌症模型——包括Transwell细胞培养、球体及在柔性细胞外基质凝胶中生长的类器官，这些模型比传统二维基底培养的细胞更能模拟正常与癌变组织的发展过程——但它们仍缺乏活体器官中细胞所经历的组织-组织界面、器官级结构、流体流动和机械信号，且难以从不同组织微区室中采集样本。本综述将阐述微流控细胞培养技术的最新进展如何推动人类器官芯片的产生，这些芯片现正被用于在体外模拟人类相关组织和器官微环境中的癌细胞行为。器官芯片使研究人员能够以受控方式单独或精确组合改变局部细胞、分子、化学及生物物理参数，同时分析这些参数如何影响人类癌症的形成、进展及治疗反应。我们还将讨论需要克服的挑战，以确保器官芯片模型满足癌症研究人员、药物开发者和关注个性化医疗的临床医生的需求。

原文链接：

Modelling cancer in microfluidic human organs-on-chips