Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-Ro, Songpa-Gu, Seoul 05505, Korea.
Asan Center for Cancer Genome Discovery, Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro, Songpa-Gu, Seoul 05505, Korea.
Lab Chip. 2019 Sep 7;19(17):2854-2865. doi: 10.1039/c9lc00496c. Epub 2019 Aug 1.
Microfluidic devices as translational research tools provide a potential alternative to animal experiments due to their ability to mimic physiological parameters. Several approaches that can be used to predict the efficacy or toxicity of anticancer drugs are available. In general, standard cell culture systems have the advantages of being relatively cost-effective, having high-throughput capability, and providing convenience. However, these models are inadequate to accurately recapitulate the complex organ-level physiological and pharmacological responses. Here, we present a one-stop microfluidic device enabling both 3-dimensional (3D) lung cancer organoid culturing and drug sensitivity tests directly on a microphysiological system (MPS). Our platform reproducibly yields 3D lung cancer organoids in a size-controllable manner and demonstrates for the first time the production of lung cancer organoids from patients with small-cell lung cancer. Lung cancer organoids derived from primary small-cell lung cancer tumors can rapidly proliferate and exhibit disease-specific characteristics in our MPS. Cisplatin and etoposide, the standard regimen for lung cancer, showed increased apoptosis induction in a concentration-dependent manner, but the organoids contained chemo-resistant cells in the core. We envision that this system may provide important information to guide therapeutic approaches at the preclinical level.
微流控装置作为转化研究工具，由于其能够模拟生理参数，因此提供了一种替代动物实验的潜在方法。有几种方法可用于预测抗癌药物的疗效或毒性。一般来说，标准细胞培养系统具有相对经济高效、高通量能力和便利性的优点。然而，这些模型不足以准确再现复杂的器官水平生理和药理反应。在这里，我们展示了一种一站式微流控装置，可直接在微生理系统（MPS）上进行 3 维（3D）肺癌类器官培养和药物敏感性测试。我们的平台以可控制的方式可重复地产生 3D 肺癌类器官，并首次展示了从小细胞肺癌患者中产生肺癌类器官的能力。源自原发性小细胞肺癌肿瘤的肺癌类器官在我们的 MPS 中能够快速增殖并表现出疾病特异性特征。顺铂和依托泊苷是肺癌的标准治疗方案，在浓度依赖性方式下显示出增加的细胞凋亡诱导作用，但类器官的核心中含有化疗耐药细胞。我们设想该系统可以在临床前水平提供重要信息以指导治疗方法。
