Kyoto University Develops Advanced Kidney Organoid Model for Improved Drug Screening

Researchers at Kyoto University have made a breakthrough in developing a human iPS cell-derived kidney organoid-based proximal tubule-on-chip (OPTECs-on-Chip) that closely mimics in vivo renal physiology. This innovative model has been found to exhibit enhanced expression and polarity of essential renal transporters, making it a powerful tool for assessing drug transport and nephrotoxicity.

Key Takeaways:

• The OPTECs-on-Chip model demonstrates significant improvements in the expression and functionality of OAT1/3 and OCT2 transporters compared to previous models using immortalized cells.
• The microphysiological system (MPS) utilizes two widely adopted differentiation protocols to derive kidney organoids, integrating them into a microfluidic system to form a proximal tubule model.
• The OPTECs-on-Chip model successfully maintains transporter expression, replicating the mechanisms of drug excretion in renal proximal tubules in vitro, mimicking the function of human epithelial tissue.
• The team anticipates applying their MPS model as a screening tool for developing new drugs by evaluating the transport and nephrotoxicity of various membrane proteins.
• The model has significant potential for drug screening and personalized medicine, with the ability to incorporate patient-derived stem cells for personalized assessments of renal transport and disease modeling.

Statistics:

• The OPTECs-on-Chip model exhibits enhanced expression and polarity of OAT1/3 and OCT2 transporters compared to previous models.
• The MPS model replicates the mechanisms of drug excretion in renal proximal tubules in vitro, mimicking the function of human epithelial tissue.
• The team demonstrated that the OPTECs-on-Chip model assesses nephrotoxicity and quantifies transcellular substrates transported specifically by OAT1, OAT3, and OCT2.
• Applications of the MPS model include drug screening and personalized medicine, with the ability to incorporate patient-derived stem cells for personalized assessments.

Sources:

• VerticalNews Health & Science
• Kyoto University
• News Reporter-Staff News Editor at VerticalNews Health & Science
• "Our OPTECs-on-Chip demonstrates significant improvements in the expression and functionality of OAT1/3 and OCT2 transporters compared to previous models using immortalized cells," Cheng Ma from KyotoU's Graduate School of Engineering
• Team leader Ryuji Yokokawa at KyotoU's Department of Micro Engineering
• "Listening to the needs of pharmaceutical companies to develop the high-function kidney chip they require is the best way for us to integrate MPS technology into drug development," Ryuji Yokokawa at KyotoU's Department of Micro Engineering.