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

Lei Yin,Guanru Du,Hongbo Zhang,Wenjun Zhang,Bing Zhang,Ruixue Yin,Shih-Mo Yang

doi:10.1038/s41598-020-63096-3

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.

Highlights

Developing and commercializing new drugs is a long and costly process
In our previous work[35], we developed a kidney environment by means of microfluidics technology for renal tubules and perivascular capillary culture
The study reported in the present paper was a continuous effort to explore the feasibility of using that system for predicting drug-induced nephrotoxicity via cisplatin (DDP), gentamycin (GM), and cyclosporin A (CsA) on the kidney chip

Summary

Introduction

Developing and commercializing new drugs is a long and costly process. Pharmaceutical companies typically spend a few decades and substantial amounts of money for drug research and development (R&D)[1]. It is highly desirable to predict drug-induced nephrotoxicity without a need of animal experiments. This could be achieved using intelligent devices called organ-on-chip. The reconstruction of an environment with renal tubular cells has attracted considerable attention in the field of microfluidics, as such an environment has a potential to imitate a real cell environment In such an environment, the fluid flows and interacts with the kidney tissue or cell to create shear stress in the tissue or cell[15,16]. Microfluidics provides an excellent tool to develop the aforementioned artificial cell environment[22,23,24] Such environments have been applied to several artificial organs such as the lung, liver, kidney, and gut[25,26]. The results of these new studies expected to build a reliable artificial kidney disease model to predict effects of drugs on human body and to complete the establishment of drug detoxification model

Methods

Results

Conclusion