Johnson Annika, Reimer Samuel, Childres Ryan, Cupp Grace, Kohs Tia C L, McCarty Owen J T, Kang Youngbok Abraham
Department of Mechanical, Civil, and Biomedical Engineering, George Fox University, 414 N. Meridian Street, #6088, Newberg, OR 97132 USA.
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239 USA.
Cell Mol Bioeng. 2022 Dec 26;16(1):3-21. doi: 10.1007/s12195-022-00755-7. eCollection 2023 Feb.
The tumor microenvironment (TME) plays a critical, yet mechanistically elusive role in tumor development and progression, as well as drug resistance. To better understand the pathophysiology of the complex TME, a reductionist approach has been employed to create microfluidic models called "tumor chips". Herein, we review the fabrication processes, applications, and limitations of the tumor chips currently under development for use in cancer research. Tumor chips afford capabilities for real-time observation, precise control of microenvironment factors (e.g. stromal and cellular components), and application of physiologically relevant fluid shear stresses and perturbations. Applications for tumor chips include drug screening and toxicity testing, assessment of drug delivery modalities, and studies of transport and interactions of immune cells and circulating tumor cells with primary tumor sites. The utility of tumor chips is currently limited by the ability to recapitulate the nuances of tumor physiology, including extracellular matrix composition and stiffness, heterogeneity of cellular components, hypoxic gradients, and inclusion of blood cells and the coagulome in the blood microenvironment. Overcoming these challenges and improving the physiological relevance of tumor models could provide powerful testing platforms in cancer research and decrease the need for animal and clinical studies.
肿瘤微环境（TME）在肿瘤的发生、发展以及耐药性方面发挥着关键作用，但其作用机制仍难以捉摸。为了更好地理解复杂的肿瘤微环境的病理生理学，人们采用了一种简化的方法来创建称为“肿瘤芯片”的微流控模型。在此，我们回顾了目前正在开发的用于癌症研究的肿瘤芯片的制造过程、应用和局限性。肿瘤芯片具备实时观察、精确控制微环境因素（如基质和细胞成分）以及施加生理相关流体剪切应力和扰动的能力。肿瘤芯片的应用包括药物筛选和毒性测试、药物递送方式评估以及免疫细胞和循环肿瘤细胞与原发性肿瘤部位的运输和相互作用研究。目前，肿瘤芯片的实用性受到重现肿瘤生理学细微差别能力的限制，这些细微差别包括细胞外基质组成和硬度、细胞成分的异质性、缺氧梯度以及血液微环境中血细胞和凝血组的纳入。克服这些挑战并提高肿瘤模型的生理相关性可为癌症研究提供强大的测试平台，并减少对动物和临床研究的需求。
