薬効毒性評価に向けた経上皮電気抵抗計測システム集積型尿細管モデルバイス

抄録

In drug discovery research, an in vitro tubule model is necessary as an alternative method of animal experiments for drug toxicity assays. Kidney-derived cells are cultured on a microporous membrane in culture inserts and evaluated with a Transepithelial Electrical Resistance (TEER) measurement which is a well-established method for quantitative observation of kinetics and monitoring tight junctions of cells in conventional methods. However, it is difficult that the in vitro tubule models with culture inserts reproduce its physiological functionality. Microfluidics is a promising technology to reproduce physiological environments and functionality on cultured cells. In this study, we have developed a microfluidic device which is capable of measuring TEER of cultured cells on a microporous membrane. Electrodes for TEER measurement have been integrated with a microfluidic device which has a culture part with a microporous membrane. To validate functions of the device, TEER value of renal cells cultured in the device has been measured. We confirmed that the TEER value increase with their proliferation. Then, the device has been used for kidney toxicity assays using model chemicals, cisplatin and cimetidine. As a result, we conclude that the device may be a powerful tool which can be applied to drug discovery researches.