Host: The Japan Society of Mechanical Engineers
Name : [in Japanese]
Date : September 08, 2019 - September 11, 2019
Renal proximal tubule epithelial cells (RPTECs) have reabsorptive and secretory functions involved in membrane transporters, and the cells are cultured in a microphysiological system for the observation of drug-induced nephrotoxicity. However, even today an effective method to recapitulate RPTEC functions in vitro has not been fully established. Since RPTECs are exposed to the flow of urine in vivo, we developed a microphysiological system in this study for the application of flow shear stress and the screening of nephrotoxicity. Micro-volumetric flow rates of a peristaltic pump were controlled through pulse-width modulation generated by a micro-computer. The cell culture device contained a tubule channel and a vascular channel, and a micro-pore membrane was sandwiched between the two layers. In this study, RPTECs were cultured on the membrane and exposed to flow shear stress at a physiological level for different time periods after pre-culture. After shear stress exposure for 3 days, cell membrane transporter MATE2-K was up-regulated, and mRNA levels of transporters OCT2, MATE1, MATE2 and P-gp increased prominently with 5-day exposure. Since nephrotoxicity is commonly elicited by injuring RPTECs, which is mediated by membrane transporters, enhanced expression of membrane transporters by flow shear stress may lead to high sensitivity of the microphysiological system.
