A Simple and Robust Microfluidic Glomerular Filtration Barrier-on-a-Chip Platform for Investigating Drug-Induced...

Area of Science:

• Nephrology
• Biomedical Engineering
• Drug Discovery

Background:

• The glomerular filtration barrier (GFB) is crucial for kidney function, filtering waste and maintaining fluid balance.
• Drug-induced nephrotoxicity, a major challenge in drug development, often involves GFB dysfunction.
• Current screening methods for nephrotoxicity are limited.

Purpose of the Study:

• To develop a simple, robust, and efficient microfluidic platform for studying the GFB.
• To create a model for assessing drug-induced nephrotoxicity and evaluating kidney disease drugs.
• To enable parallelized drug screening under physiological conditions.

Main Methods:

• A microfluidic chip (GFB-on-a-chip, GFBoC) was designed using the SLAS standard format.
• The GFB was reconstructed using human glomerular mesangial cells, podocytes, and glomerular endothelial cells on a transwell membrane.
• The GFBoC allowed pump-/tubing-less perfusion culture and off-chip bioanalysis.

Main Results:

• The GFBoC successfully mimicked glomerular selective permeability, demonstrated by albumin filtration and leakage studies.
• The model effectively showed the detrimental effects of the drug doxorubicin on the GFB.
• The platform facilitated parallel experiments with moderate operational complexity.

Conclusions:

• The GFBoC is a promising, simple, and robust platform for high-throughput nephrotoxicity testing.
• This model can accelerate the development of safer therapeutics and kidney disease treatments.
• The GFBoC facilitates efficient parallel testing of multiple drugs and kidney disease therapies.