Yu Fang, Goh Yeek Teck, Li Huan, Chakrapani Narmada Balakrishnan, Ni Ming, Xu Guo Lin, Hsieh Tseng-Ming, Toh Yi-Chin, Cheung Christine, Iliescu Ciprian, Yu Hanry
Institute of Bioengineering and Nanotechnology, ASTAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669.
Institute of Molecular and Cell Biology, ASTAR, Proteos, 61 Biopolis Drive, Singapore 138673.
Biomicrofluidics. 2020 May 27;14(3):034108. doi: 10.1063/5.0004286. eCollection 2020 May.
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 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 screening of nutraceuticals using hPSC-derived cells.
人多能干细胞（hPSC）是用于生成用于药物疗效测试的细胞衍生物的重要资源。营养保健品的代谢产物可对血管产生抗炎作用。然而，hPSC衍生的肝细胞（hPSC-HEPs）中产生的营养保健品代谢产物浓度通常较低。为了能够在这种环境下检测这些代谢产物，我们开发了一种共培养模型，该模型由平行共培养室和具有最小液体体积的循环微流控系统组成，可提供最佳细胞培养环境。该模型使细胞能够持续暴露于营养保健品代谢产物中。在这种灌注培养模型中，hPSC衍生的内皮细胞和hPSC-HEPs在没有物理接触的情况下进行共培养。当向共培养物中加入抗炎营养保健品槲皮素时，与静态对照相比，芯片上检测到的槲皮素代谢产物水平更高。我们在共培养模型中用白细胞介素-1β进一步诱导炎症，并测量白细胞介素8（IL-8）的产生。与静态培养相比，灌注共培养中槲皮素代谢产物对IL-8水平的抑制作用更显著。这是由于芯片上代谢产物产量的提高。这种微流控共培养模型能够使用hPSC衍生的细胞筛选营养保健品。
