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A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice

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Abstract

Diabetic nephropathy is a major chronic renal complication of diabetes mellitus, and is the leading cause of end-stage kidney diseases. Establishing a disease model of diabetic nephropathy in vitro can accelerate the understanding of its mechanisms and pharmaceutical development. We provide the proof-of-principle for using a glomerulus-on-a-chip microdevice that reconstitutes organ-level kidney functions to create a human disease model of early stage diabetic nephropathy on chip. The microfluidic device, which recapitulates the glomerular microenvironment, consists of parallel channels lined by isolated primary glomerular microtissues that experience fluid flow to mimic the glomerular filtration barrier (GFB), including glomerular endothelial cells, 3D basement membrane and podocytes. This device was used to reproduce high glucose-induced critical pathological responses in diabetic nephropathy as observed in humans. The results reveal that hyperglycemia plays a crucial role in the development of increased barrier permeability to albumin and glomerular dysfunction that lead to proteinuria. This organ-on-a-chip microdevice mimics the critical pathological responses of glomerulus that are characteristic of diabetic nephropathy that has not been possible by cell-based and animal models, providing a useful platform for studying the mechanism of diabetic nephropathy and developing an effective therapy in glomerular diseases.

Graphical abstract: A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice

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Publication details

The article was received on 09 Feb 2017, accepted on 04 Apr 2017 and first published on 10 Apr 2017


Article type: Paper
DOI: 10.1039/C7LC00134G
Citation: Lab Chip, 2017, Advance Article
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    A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice

    L. Wang, T. Tao, W. Su, H. Yu, Y. Yu and J. Qin, Lab Chip, 2017, Advance Article , DOI: 10.1039/C7LC00134G

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