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

Astgik Petrosyan, Paolo Cravedi, Valentina Villani, Andrea Angeletti, Joaquin Manrique, Alessandra Renieri, Roger E. De Filippo, Laura Perin () and Stefano Da Sacco ()
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Astgik Petrosyan: Children’s Hospital Los Angeles
Paolo Cravedi: Icahn School of Medicine at Mount Sinai
Valentina Villani: Children’s Hospital Los Angeles
Andrea Angeletti: University of Bologna
Joaquin Manrique: Complejo Hospitalario de Navarra
Alessandra Renieri: Azienda Ospedaliera Universitaria Senese
Roger E. De Filippo: Children’s Hospital Los Angeles
Laura Perin: Children’s Hospital Los Angeles
Stefano Da Sacco: Children’s Hospital Los Angeles

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11577-z

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