The lymphatic system is a complex organ system that is essential in regulating the development of host immune responses. Because of the complexity of the lymphatic system and the existence of few in vitro models that replicate human lymphatic vessels, there is a need for a primary cell-based lymphatic model that can provide a better understanding of the effects of flow parameters, therapeutics, and other stimuli on lymphatic vessel behavior. In this report, a fluidic device models the cyclical lymphatic flow under normal and disease conditions. The device utilizes a pumpless design, operating with gravitational forces to simulate normal conditions with a shear of 0.092 Pa (0.92 dyn/cm²) as well as disease conditions with an increased shear of (0.67 Pa, 6.7 dyn/cm²). The cyclical pumping present in lymphatic vessels is replicated by applying shear stress for a period of 10 s multiple times per minute. Primary human lymphatic endothelial cells (HLECs) cultured in the device for 10 days produce less interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-α) per cell than cells cultured under static conditions. The results are consistent with previously published in vivo measurements, indicating that the fluidic device mimics conditions for IL-8 and TNF-α expression well. Data obtained with the devices also indicate that primary HLECs proliferate faster under high-shear than under low-shear conditions.

中文翻译：

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具有暴露于循环流体流动能力的芯片上淋巴管

淋巴系统是一个复杂的器官系统，对调节宿主免疫反应的发展至关重要。由于淋巴系统的复杂性和复制人体淋巴管的体外模型很少，因此需要一种基于原代细胞的淋巴模型，可以更好地理解流动参数、治疗和其他对淋巴管行为的刺激。在本报告中，流体装置模拟了正常和疾病条件下的循环淋巴流动。该装置采用无泵设计，在重力作用下运行以模拟剪切力为 0.092 Pa (0.92 dyn/cm ² ) 的正常条件以及剪切力增加 (0.67 Pa, 6.7 dyn/cm 2 ) 的疾病^条件）。通过每分钟多次施加 10 秒的剪切应力来复制存在于淋巴管中的周期性泵送。在该装置中培养 10 天的原代人淋巴管内皮细胞 (HLEC) 每细胞产生的白细胞介素 8 (IL-8) 和肿瘤坏死因子 α (TNF-α) 比在静态条件下培养的细胞少。结果与先前发表的体内测量结果一致，表明流体装置很好地模拟了 IL-8 和 TNF-α 表达的条件。使用这些设备获得的数据还表明，初级 HLEC 在高剪切条件下的增殖速度比在低剪切条件下快。