New kidney chip offers breakthrough for drug development and personalized medicine

The development of advanced drug screening tools is crucial for advancing personalized medicine and developing more effective treatments. One organ receiving particular attention in this area is the kidney.

For example, the kidney proximal tubules are essential for the reabsorption of important substances from the bloodstream before urine formation. Traditional in vitro Models have difficulty replicating this accurately because they often do not express important transport proteins, such as organic anion transporters — OAT1/3 — and organic cation transporter 2 — 2 OCT.

A team from Kyoto University has now Human iPS cell-derived kidney organoid based on a proximal tubule-on-chip — OPTECs-on-Chip — that imitates in vivo Renal physiology is more accurate than ever before. This model features improved expression and polarity of key renal transporters, making it a powerful tool for assessing drug transport and nephrotoxicity.

Our OPTECs-on-chip shows significant improvements in the expression and functionality of OAT1/3 and OCT2 transporters compared to previous models using immortalized cells.”

Cheng Ma, Graduate School of Engineering, Kyoto University

The microphysiological system — MPS — uses two widely used differentiation protocols to generate kidney organoids and integrates them into a microfluidic system to form a proximal tubule model, successfully maintaining transporter expression and reproducing the mechanisms of drug excretion in renal proximal tubules. in vitrowhich mimics the function of human epithelial tissue.

“Responding to the needs of pharmaceutical companies and developing the highly functional kidney chip they require is the best way for us to integrate MPS technology into drug development,” explains team leader Ryuji Yokokawa of the Department of Microengineering at KyotoU.

“We have shown that our OPTECs-on-chip not only assesses nephrotoxicity but also quantifies transcellular substrates specifically transported by OAT1, OAT3 and OCT2. This underlines the advantages of using iPS cells and a microfluidic system for replication in vivo cellular transport mechanisms,” add co-author Minoru Takasato of the RIKEN Center for Biosystems Dynamics Research together with Toshikazu Araoka of the Center for iPS Cell Research and Application at Kyoto University.

Yokokawa's team expects to be able to use their MPS model as a screening tool for new drug development by studying the transport and nephrotoxicity of various membrane proteins.

“Our model has great potential for drug screening and personalized medicine,” notes Yokokawa. “By incorporating the patient's own stem cells, we can develop personalized assessments for renal transport and disease modeling.”