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

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 capillar...

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Autores principales: Petrosyan, Astgik, Cravedi, Paolo, Villani, Valentina, Angeletti, Andrea, Manrique, Joaquin, Renieri, Alessandra, De Filippo, Roger E., Perin, Laura, Da Sacco, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692336/
https://www.ncbi.nlm.nih.gov/pubmed/31409793
http://dx.doi.org/10.1038/s41467-019-11577-z
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author Petrosyan, Astgik
Cravedi, Paolo
Villani, Valentina
Angeletti, Andrea
Manrique, Joaquin
Renieri, Alessandra
De Filippo, Roger E.
Perin, Laura
Da Sacco, Stefano
author_facet Petrosyan, Astgik
Cravedi, Paolo
Villani, Valentina
Angeletti, Andrea
Manrique, Joaquin
Renieri, Alessandra
De Filippo, Roger E.
Perin, Laura
Da Sacco, Stefano
author_sort Petrosyan, Astgik
collection PubMed
description 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.
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spelling pubmed-66923362019-08-15 A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier Petrosyan, Astgik Cravedi, Paolo Villani, Valentina Angeletti, Andrea Manrique, Joaquin Renieri, Alessandra De Filippo, Roger E. Perin, Laura Da Sacco, Stefano Nat Commun Article 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. Nature Publishing Group UK 2019-08-13 /pmc/articles/PMC6692336/ /pubmed/31409793 http://dx.doi.org/10.1038/s41467-019-11577-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Petrosyan, Astgik
Cravedi, Paolo
Villani, Valentina
Angeletti, Andrea
Manrique, Joaquin
Renieri, Alessandra
De Filippo, Roger E.
Perin, Laura
Da Sacco, Stefano
A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier
title A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier
title_full A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier
title_fullStr A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier
title_full_unstemmed A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier
title_short A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier
title_sort glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692336/
https://www.ncbi.nlm.nih.gov/pubmed/31409793
http://dx.doi.org/10.1038/s41467-019-11577-z
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