Year: 2019
Type: article
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.
Source: Nature Communications
Institutions: Children's Hospital Los Angeles, Saban Research Institute, Icahn School of Medicine at Mount Sinai, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, University of Bologna, Complejo Hospitalario de Navarra, Azienda Ospedaliera Universitaria Senese, University of Southern California
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Award: G1940986629
OpenAlex ID: W2967299926