Lee Philip J, Hung Paul J, Lee Luke P
Department of Bioengineering, Biomolecular Nanotechnology Center, Berkeley Sensor and Actuator Center, University of California-Berkeley, Berkeley, CA 94720-1762, USA.
Biotechnol Bioeng. 2007 Aug 1;97(5):1340-6. doi: 10.1002/bit.21360.
Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial liver sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the liver acinus. This unit consisted of a cord of hepatocytes (50 x 30 x 500 microm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min). This configuration sustained rat and human hepatocytes for 7 days without an extracellular matrix (ECM) coating. Experiments with the metabolism mediated liver toxicant diclofenac showed no hepatotoxicity after 4 h and an IC(50) of 334 +/- 41 microM after 24 h.
原代肝细胞是药物毒性筛选的生理相关模型。在此，我们构建了一种受生物启发的人工肝血窦，其具有类似微流体内皮细胞的屏障，具有与肝腺泡相似的物质运输特性。该单元由一束肝细胞（50×30×500微米）组成，营养物质通过对流运输容器（10纳升/分钟）经类似微流体内皮细胞的屏障扩散提供给肝细胞。这种结构在没有细胞外基质（ECM）包被的情况下使大鼠和人肝细胞维持了7天。用代谢介导的肝毒物双氯芬酸进行的实验显示，4小时后无肝毒性，24小时后的半数抑制浓度（IC50）为334±41微摩尔。
