[Development of novel culture system using nano-biotechnology]

We have developed two cell culture systems for use in pharmaceutical research using nano-biotechnology. First, we developed a double layered co-culture system using cell sheet technology, and showed that in a layered co-culture system with HepG2 and bovine endothelial cells, the expression levels of various cytochrome P450 (CYP) genes were significantly increased compared to monolayer cultured HepG2 cells. In the layered HepG2 co-culture, expression of the CYP2C and CYP3A family genes was induced by phenobarbital treatment. We also detected CYP3A4 enzyme induction using this co-culture system. Next, we developed sensor cells. Living cells maintain homeostasis by responding quickly and with great sensitivity to changes in the external environment. Consequently, sensors using cells as active elements are thought to be able to perform analyses faster and with more sensitivity than previous methods. We have modified mammalian cells using genetic engineering techniques to develop next-generation cell sensors that can visually represent specific reactions. We successfully produced devices using sensor cells that can process a variety of specimens using Micro-Electro-Mechanical System (MEMS), Nano-Electro-Mechanical System (NEMS), and other nano/micro processing technologies. These systems may serve as a useful model for in vitro pharmacological studies on the coordinated regulation of metabolism and cytotoxicity. In this review, we introduce our research and describe recent trends in this field.