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A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier.

Nature communications (2019-08-15)
Astgik Petrosyan, Paolo Cravedi, Valentina Villani, Andrea Angeletti, Joaquin Manrique, Alessandra Renieri, Roger E De Filippo, Laura Perin, Stefano Da Sacco
ABSTRACT

In this work we model the glomerular filtration barrier, the structure responsible for filtering the blood and preventing the loss of proteins, using human podocytes and glomerular endothelial cells seeded into microfluidic chips. In long-term cultures, cells maintain their morphology, form capillary-like structures and express slit diaphragm proteins. This system recapitulates functions and structure of the glomerulus, including permselectivity. When exposed to sera from patients with anti-podocyte autoantibodies, the chips show albuminuria proportional to patients' proteinuria, phenomenon not observed with sera from healthy controls or individuals with primary podocyte defects. We also show its applicability for renal disease modeling and drug testing. A total of 2000 independent chips were analyzed, supporting high reproducibility and validation of the system for high-throughput screening of therapeutic compounds. The study of the patho-physiology of the glomerulus and identification of therapeutic targets are also feasible using this chip.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
IgG from human serum, reagent grade, ≥95% (HPLC), buffered aqueous solution
Sigma-Aldrich
Anti-PLA2R Antibody, clone 5F5.1, clone 5F5.1, from mouse

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