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Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System

There is a lack of physiologically relevant in vitro human kidney models for disease modelling and detecting drug-induced effects given the limited choice of cells and difficulty implementing quasi-physiological culture conditions. We investigated the influence of fluid shear stress on primary human...

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Autores principales: Specioso, Gabriele, Bovard, David, Zanetti, Filippo, Maranzano, Fabio, Merg, Céline, Sandoz, Antonin, Titz, Bjoern, Dalcanale, Federico, Hoeng, Julia, Renggli, Kasper, Suter-Dick, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598399/
https://www.ncbi.nlm.nih.gov/pubmed/36290484
http://dx.doi.org/10.3390/bioengineering9100516
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author Specioso, Gabriele
Bovard, David
Zanetti, Filippo
Maranzano, Fabio
Merg, Céline
Sandoz, Antonin
Titz, Bjoern
Dalcanale, Federico
Hoeng, Julia
Renggli, Kasper
Suter-Dick, Laura
author_facet Specioso, Gabriele
Bovard, David
Zanetti, Filippo
Maranzano, Fabio
Merg, Céline
Sandoz, Antonin
Titz, Bjoern
Dalcanale, Federico
Hoeng, Julia
Renggli, Kasper
Suter-Dick, Laura
author_sort Specioso, Gabriele
collection PubMed
description There is a lack of physiologically relevant in vitro human kidney models for disease modelling and detecting drug-induced effects given the limited choice of cells and difficulty implementing quasi-physiological culture conditions. We investigated the influence of fluid shear stress on primary human renal proximal tubule epithelial cells (RPTECs) cultured in the micro-physiological Vitrofluid device. This system houses cells seeded on semipermeable membranes and can be connected to a regulable pump that enables controlled, unidirectional flow. After 7 days in culture, RPTECs maintained physiological characteristics such as barrier integrity, protein uptake ability, and expression of specific transporters (e.g., aquaporin-1). Exposure to constant apical side flow did not cause cytotoxicity, cell detachment, or intracellular reactive oxygen species accumulation. However, unidirectional flow profoundly affected cell morphology and led to primary cilia lengthening and alignment in the flow direction. The dynamic conditions also reduced cell proliferation, altered plasma membrane leakiness, increased cytokine secretion, and repressed histone deacetylase 6 and kidney injury molecule 1 expression. Cells under flow also remained susceptible to colistin-induced toxicity. Collectively, the results suggest that dynamic culture conditions in the Vitrofluid system promote a more differentiated phenotype in primary human RPTECs and represent an improved in vitro kidney model.
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spelling pubmed-95983992022-10-27 Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System Specioso, Gabriele Bovard, David Zanetti, Filippo Maranzano, Fabio Merg, Céline Sandoz, Antonin Titz, Bjoern Dalcanale, Federico Hoeng, Julia Renggli, Kasper Suter-Dick, Laura Bioengineering (Basel) Article There is a lack of physiologically relevant in vitro human kidney models for disease modelling and detecting drug-induced effects given the limited choice of cells and difficulty implementing quasi-physiological culture conditions. We investigated the influence of fluid shear stress on primary human renal proximal tubule epithelial cells (RPTECs) cultured in the micro-physiological Vitrofluid device. This system houses cells seeded on semipermeable membranes and can be connected to a regulable pump that enables controlled, unidirectional flow. After 7 days in culture, RPTECs maintained physiological characteristics such as barrier integrity, protein uptake ability, and expression of specific transporters (e.g., aquaporin-1). Exposure to constant apical side flow did not cause cytotoxicity, cell detachment, or intracellular reactive oxygen species accumulation. However, unidirectional flow profoundly affected cell morphology and led to primary cilia lengthening and alignment in the flow direction. The dynamic conditions also reduced cell proliferation, altered plasma membrane leakiness, increased cytokine secretion, and repressed histone deacetylase 6 and kidney injury molecule 1 expression. Cells under flow also remained susceptible to colistin-induced toxicity. Collectively, the results suggest that dynamic culture conditions in the Vitrofluid system promote a more differentiated phenotype in primary human RPTECs and represent an improved in vitro kidney model. MDPI 2022-09-30 /pmc/articles/PMC9598399/ /pubmed/36290484 http://dx.doi.org/10.3390/bioengineering9100516 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Specioso, Gabriele
Bovard, David
Zanetti, Filippo
Maranzano, Fabio
Merg, Céline
Sandoz, Antonin
Titz, Bjoern
Dalcanale, Federico
Hoeng, Julia
Renggli, Kasper
Suter-Dick, Laura
Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System
title Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System
title_full Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System
title_fullStr Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System
title_full_unstemmed Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System
title_short Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System
title_sort apical medium flow influences the morphology and physiology of human proximal tubular cells in a microphysiological system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598399/
https://www.ncbi.nlm.nih.gov/pubmed/36290484
http://dx.doi.org/10.3390/bioengineering9100516
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