Effect of shear stress on the proximal tubule-on-a-chip for multi-organ microphysiological system

A multi-organ-on-a-chip (MOC) can be used to induce specific diseases and utilize the absorption, distribution, metabolism, and excretion properties of drugs to enable the prediction and analysis of the drug efficacy in the disease. As a first step to realize the MOC, renal proximal tubular epithelial cells (RPTECs) were cultured on a MOC based on gravity flow to evaluate their excretion function by varying shear stresses. Normal shear stress (0.13 dyne/cm 2 ) and 1.5 and 2 times shear stresses were applied, and the cell viability, transepithelial electrical resistance, glucose reabsorption, and permeability were quantitatively compared. We confirmed the gene expressions of the drug transporters, conducted a pharmacokinetic (PK) test using metformin, and confirmed the diastolic function of the drug, which is one of the main functions of the RPTECs. The results confirmed that the reabsorption and excretion of the RPTEC were well reproduced and could be adjusted by the shear stress. It is expected that this will be able to play a role in achieving the complete excretion function from the MOC in future new drug development.