A Three-Layer Microfluidic Kidney Chip for Drug Nephrotoxicity Test

Nowadays, in the preclinical and clinical studies of drugs, cell culture in petri dishes and animal experiments still can’t adequately reflect the effects of new drugs on human kidneys, which highlights a great need to develop a model with high accuracy to recapitulate organ function in vitro. Here, a three-layer microfluidic kidney chip that can be used to mimic the structure and function of kidneys by integrating polydimethyl siloxy (PDMS) microfluidic channels and porous membranes. We also developed a supporting microfluidic culture platform for the long-term culture of kidney cells. On this basis, two types of cell lines (renal proximal tubular epithelial cells, RPTECs, and peritubular capillary endothelial cells, PCECs) and three types of drugs (ciplatin, DDP, gentamycin, GM, and cyclosporine A, CsA) were used for accurate assessment of drug-induced nephrotoxicity. Considered of the effects of time, we also tested two dosing regimens of GM. Cells were under the fluidic shear stress of continuous flow to mimic the pharmacokinetics of single injection and continuous infusion. Unlike in petri dishes, cells cultured in the microfluidic kidney chips had a better performance on both the cell growth and the drug nephrotoxicity evaluation. The microfluidic devices presented here may be useful to mimic the renal tubular system in vitro for evaluating drug nephrotoxicity during preclinical studies.