在微流体系统中进行长期监测，以研究肿瘤球体对慢性和循环性缺氧的反应。,Scientific Reports

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在微流体系统中进行长期监测，以研究肿瘤球体对慢性和循环性缺氧的反应。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-11-28 , DOI: 10.1038/s41598-019-54001-8
Samantha M Grist ₁ , S Soroush Nasseri ₁ , Loïc Laplatine ₁ , Jonathan C Schmok ₁ , Dickson Yao ₁ , Jessica Hua ₁ , Lukas Chrostowski ₁ , Karen C Cheung ₁

Affiliation

我们证明了时空氧气控制和长期显微镜监测相结合的微流控平台的应用，以观察肿瘤球体对缺氧的反应。该平台能够重现传统细胞培养环境中无法达到的与生理相关的低氧和循环氧水平，而基于图像的监测则可以可视化细胞对这些与生理相关的状况的反应。在低氧暴露过程中监测球状体的培养，使我们首次观察到球状体的膨胀和收缩是响应于氧气在0％和10％之间变化的时变氧分布。这种溶胀-收缩行为似乎是由球体内单个细胞的溶胀驱动的。我们还将该系统应用于在各种氧气条件下进行抗癌治疗期间监测肿瘤模型。我们观察到，在循环性低氧情况下，抗癌药阿霉素的摄取要比在慢性低氧或体外常氧状态下的摄取高，并且我们系统促进的双光子显微镜监测也使我们能够观察到单球体中球体对阿霉素摄取的异质性。细胞水平。将光学切片显微镜与精确的时空氧气控制和3D培养相结合，为未来有关驱动癌症进展和抗癌治疗耐药性的微环境机制的广泛研究打开了大门。这些类型的研究可以促进癌症诊断和治疗的未来改进。并且我们系统促进的双光子显微镜监控也使我们能够在单细胞水平上观察球体中阿霉素吸收的异质性。将光学切片显微镜与精确的时空氧气控制和3D培养相结合，为未来有关驱动癌症进展和抗癌治疗耐药性的微环境机制的广泛研究打开了大门。这些类型的研究可以促进癌症诊断和治疗的未来改进。并且我们系统促进的双光子显微镜监控也使我们能够在单细胞水平上观察球体中阿霉素吸收的异质性。将光学切片显微镜与精确的时空氧气控制和3D培养相结合，为未来有关驱动癌症进展和抗癌治疗耐药性的微环境机制的广泛研究打开了大门。这些类型的研究可以促进癌症诊断和治疗的未来改进。将光学切片显微镜与精确的时空氧气控制和3D培养相结合，为未来有关驱动癌症进展和抗癌治疗耐药性的微环境机制的广泛研究打开了大门。这些类型的研究可以促进癌症诊断和治疗的未来改进。将光学切片显微镜与精确的时空氧气控制和3D培养相结合，为未来有关驱动癌症发展和抗癌治疗的微环境机制的广泛研究打开了大门。这些类型的研究可以促进癌症诊断和治疗的未来改进。

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Long-term monitoring in a microfluidic system to study tumour spheroid response to chronic and cycling hypoxia.

We demonstrate the application of a microfluidic platform combining spatiotemporal oxygen control and long-term microscopy monitoring to observe tumour spheroid response to hypoxia. The platform is capable of recreating physiologically-relevant low and cycling oxygen levels not attainable in traditional cell culture environments, while image-based monitoring visualizes cell response to these physiologically-relevant conditions. Monitoring spheroid cultures during hypoxic exposure allows us to observe, for the first time, that spheroids swell and shrink in response to time-varying oxygen profiles switching between 0% and 10% O2; this swelling-shrinkage behaviour appears to be driven by swelling of individual cells within the spheroids. We also apply the system to monitoring tumour models during anticancer treatment under varying oxygen conditions. We observe higher uptake of the anticancer agent doxorubicin under a cycling hypoxia profile than under either chronic hypoxia or in vitro normoxia, and the two-photon microscopy monitoring facilitated by our system also allows us to observe heterogeneity in doxorubicin uptake within spheroids at the single-cell level. Combining optical sectioning microscopy with precise spatiotemporal oxygen control and 3D culture opens the door for a wide range of future studies on microenvironmental mechanisms driving cancer progression and resistance to anticancer therapy. These types of studies could facilitate future improvements in cancer diagnostics and treatment.

更新日期：2019-11-29

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