Development of Drug Efficacy Testing Platform for Glomerulonephritis

被引:1
|
作者
Kwon, Eun-Jeong [1 ]
Choi, Yunyeong [1 ]
Kim, Shin Young [1 ]
Park, Seokwoo [1 ]
Yun, Giae [1 ]
Min, Sei Hong [1 ]
Kim, Sejoong [1 ,2 ]
机构
[1] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Seongnam Si 13620, South Korea
[2] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 03080, South Korea
基金
新加坡国家研究基金会;
关键词
3D glomeruli tissue chip; glomerular filtration barrier mimicking chip; drug efficacy platform; MN chip; PODOCYTES; CULTURE;
D O I
10.3390/mi15030317
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
We developed a 3D glomeruli tissue chip for glomerulonephritis (GN) testing, featuring a gravity-driven glomerular filtration barrier (GFB) with human podocytes and endothelial cells with a bidirectional flow in the bottom channel. Using puromycin-induced GN, we observed decreased cell viability, increased albumin permeability, and reduced WT1 and nephrin compared to the normal GFB. Tacrolimus restored cell viability, reduced albumin permeability, and increased WT1 expression. Using serum from five membranous nephropathy (MN) patients, we created MN models using a GFB-mimicking chip. A notable decline in cell viability was observed in the serum-induced MN1 and MN2 models. However, tacrolimus restored it. Albumin permeability was reduced in the MN1, MN2, and MN5 models by tacrolimus treatment. MN1 displayed the best clinical response to tacrolimus, exhibiting increased expression of WT1 in chip-based evaluations after tacrolimus treatment. We successfully evaluated the efficacy of tacrolimus using puromycin-induced and serum-induced GN models on a chip that mimicked the structure and function of the GFB. The GFB-mimicking chip holds promise as a personalized platform for assessing drug efficacy using patient serum samples.
引用
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页数:14
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