Development of Drug Efficacy Testing Platform for Glomerulonephritis

Area of Science:

• Biomedical Engineering
• Nephrology
• Drug Discovery

Background:

• Glomerulonephritis (GN) and membranous nephropathy (MN) are kidney diseases affecting the glomerular filtration barrier (GFB).
• Current testing methods for GN and MN lack patient-specific models for drug efficacy evaluation.

Purpose of the Study:

• To develop and validate a 3D glomeruli tissue chip for modeling GN and MN.
• To assess the therapeutic efficacy of tacrolimus in GN and MN models using the developed chip.
• To evaluate the potential of the chip as a personalized drug testing platform.

Main Methods:

• Development of a gravity-driven 3D glomeruli tissue chip with a human GFB.
• Induction of GN using puromycin and MN using patient serum in the chip models.
• Assessment of cell viability, albumin permeability, and protein expression (WT1, nephrin).
• Evaluation of tacrolimus treatment effects on disease markers.

Main Results:

• Puromycin-induced GN model showed decreased cell viability, increased albumin permeability, and reduced WT1/nephrin.
• Tacrolimus treatment restored cell viability, reduced albumin permeability, and increased WT1 in GN models.
• Serum-induced MN models exhibited reduced cell viability, which was restored by tacrolimus.
• Tacrolimus treatment decreased albumin permeability in specific MN models (MN1, MN2, MN5) and increased WT1 expression in MN1.

Conclusions:

• The 3D glomeruli tissue chip successfully mimics the GFB structure and function for GN and MN modeling.
• The chip platform effectively evaluated tacrolimus efficacy in both puromycin-induced and patient serum-induced kidney disease models.
• This GFB-mimicking chip shows significant potential for personalized drug efficacy assessment using patient-derived samples.