Human pluripotent stem cell (hPSC) is a great resource for generating cell derivatives for drug efficiency testing. Metabolites of nutraceuticals can exert anti-inflammatory effects on blood vessels. However, the concentration of nutraceutical metabolites produced in hPSC-derived hepatocytes (hPSC-HEPs) is usually low. To enable the detection of these metabolites under the in vitro environment, we have developed a co-culture model consisting of parallel co-culture chambers and a recirculating microfluidic system with minimum fluid volume, optimal cell culture environment. The model allows cells to be exposed continuously to nutraceutical metabolites. In this perfused culturing model, hPSC-derived endothelial cells and hPSC-HEPs are co-cultured without physical contact. When an anti-inflammatory nutraceutical, quercetin, was administrated to the co-culture, higher levels of quercetin metabolites were detected on-chip compared with static control. We further induced inflammation with Interleukin-1β in the co-culture model and measured interleukin 8 (IL-8) generation. The IL-8 level was suppressed more significantly by quercetin metabolites in the perfusion co-culture, as compared to static culture. This is due to enhanced metabolites production on-chip. This microfluidic co-culture model enables in vitro screening of nutraceuticals using hPSC-derived cells.

中文翻译：

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一种血管-肝脏芯片，用于灵敏检测人类多能干细胞衍生物的营养代谢物。


人类多能干细胞 (hPSC) 是生成用于药效测试的细胞衍生物的重要资源。营养保健品的代谢物可以对血管发挥抗炎作用。然而，hPSC 源性肝细胞 (hPSC-HEP) 中产生的营养代谢物的浓度通常较低。为了能够在体外环境下检测这些代谢物，我们开发了一种共培养模型，该模型由平行共培养室和循环微流体系统组成，具有最小的流体体积和最佳的细胞培养环境。该模型允许细胞持续暴露于营养代谢物。在此灌注培养模型中，hPSC 衍生的内皮细胞和 hPSC-HEP 在没有物理接触的情况下共培养。当将抗炎营养药物槲皮素添加到共培养物中时，与静态对照相比，在芯片上检测到更高水平的槲皮素代谢物。我们进一步在共培养模型中用白细胞介素 1β 诱导炎症，并测量白细胞介素 8 (IL-8) 的生成。与静态培养相比，灌注共培养中槲皮素代谢物更显着地抑制 IL-8 水平。这是由于芯片上代谢物生产的增强。这种微流体共培养模型能够使用 hPSC 衍生细胞对营养保健品进行体外筛选。