Efficient Drug Screening and Nephrotoxicity Assessment on Co-culture Microfluidic Kidney Chip

Abstract

The function and susceptibility of various drugs are tested with renal proximal tubular epithelial cells; yet, replicating the morphology and kidneys function using the currently available in vitro models remains difficult. To overcome this difficulty, in the study presented in this paper, a device and a three-layer microfluidic chip were developed, which provides a simulated environment for kidney organs. This device includes two parts: (1) microfluidic drug concentration gradient generator and (2) a flow-temperature controlled platform for culturing of kidney cells. In chip study, renal proximal tubular epithelial cells (RPTECs) and peritubular capillary endothelial cells (PCECs) were screened with the drugs to assess the drug-induced nephrotoxicity. Unlike cells cultured in petri dishes, cells cultured in the microfluidic device exhibited higher performance in terms of both cell growth and drug nephrotoxicity evaluation. It is worth mentioning that a significant decrease in cisplatin-induced nephrotoxicity was found because of the intervention of cimetidine in the microfluidic device. In conclusion, the different in the cell performance between the microfluidic device and the petri dishes demonstrates the physiological relevance of the nephrotoxicity screening technology along with the microfluidic device developed in this study. Furthermore, this technology can also facilitate the development of reliable kidney drugs and serve as a useful and efficient test-bed for further investigation of the drug nephrotoxicity evaluation.