(1086-C) Revolutionizing Renal Research: Microfluidic Kidney Tubuloids-on-a-Chip for Improved Drug Translation
Tuesday, February 6, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: Current 2D in vitro models of renal epithelium lack the key features of the in vivo setting, such as tubular structure and perfusion, resulting in low translatability to human situations and failure in clinical translation. Microfluidic techniques are becoming increasingly recognized as a valuable tool for adding physiologically relevant cues to traditional cell cultures. These cues include long-term gradient stability and continuous perfusion. Microfluidic technology also allows for the patterning of cell layers as stratified co-cultures that are free from artificial membranes, enabling the capture of complex tissue architectures found in vivo. Here, we introduce the OrganoPlate microfluidic platform, which can accommodate up to 64 independent microfluidic chips in a microtiter plate format, allowing the growth of 64 independent kidney tubuloid-derived barrier tissues in the form of perfused tubules. These renal tubules can be formed in just four days of culture in the device showing rapid and reproducible cell polarization, tight junction formation and proper expression of renal markers. When integrated into an OrganoPlate system, kidney tubuloids form leak-tight, perfusable tubes with stable Trans Epithelial Electrical Resistance (TEER), and are suitable for high-throughput screening of compound effects through assessment of barrier integrity by use of OrganoTEER and by real-time imaging of transport. OrganoPlate grown kidney tubes treated with Pgp inhibitor Verapamil show significant reduction of Rhodamine123 transport through kidney tubule barrier which confirms show stable activity of Pgp transporter and usability of the model in studying renal drug clearance. Our results demonstrate the suitability of our in vitro microfluidic kidney tubuloid-on-a-chip model in mimicking key physiological aspects of the kidney and offer new ways for studying organ physiology and renal disease mechanisms and drug toxicity.