Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium

Abstract The human bronchial epithelium is the first line of defense against atmospheric particles, pollutants, and respiratory pathogens such as the novel SARS-CoV-2. The epithelial cells form a tight barrier and secrete proteins that are major components of the mucosal immune response. Functional...

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Autores principales:	Daniel Sanchez-Guzman, Sonja Boland, Oliver Brookes, Claire Mc Cord, René Lai Kuen, Valentina Sirri, Armelle Baeza Squiban, Stéphanie Devineau
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8c85b49ef2a94a1ea94ba083387fcfe0
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spelling	oai:doaj.org-article:8c85b49ef2a94a1ea94ba083387fcfe02021-12-02T17:04:36ZLong-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium10.1038/s41598-021-86037-02045-2322https://doaj.org/article/8c85b49ef2a94a1ea94ba083387fcfe02021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86037-0https://doaj.org/toc/2045-2322Abstract The human bronchial epithelium is the first line of defense against atmospheric particles, pollutants, and respiratory pathogens such as the novel SARS-CoV-2. The epithelial cells form a tight barrier and secrete proteins that are major components of the mucosal immune response. Functional in vitro models of the human lung are essential for screening the epithelial response and assessing the toxicity and barrier crossing of drugs, inhaled particles, and pollutants. However, there is a lack of models to investigate the effect of chronic exposure without resorting to animal testing. Here, we developed a 3D model of the human bronchial epithelium using Calu-3 cell line and demonstrated its viability and functionality for 21 days without subculturing. We investigated the effect of reduced Fetal Bovine Serum supplementation in the basal medium and defined the minimal supplementation needed to maintain a functional epithelium, so that the amount of exogenous serum proteins could be reduced during drug testing. The long-term evolution of the epithelial cell secretome was fully characterized by quantitative mass spectrometry in two preclinical models using Calu-3 or primary NHBE cells. 408 common secreted proteins were identified while significant differences in protein abundance were observed with time, suggesting that 7–10 days are necessary to establish a mature secretome in the Calu-3 model. The associated Reactome pathways highlight the role of the secreted proteins in the immune response of the bronchial epithelium. We suggest this preclinical 3D model can be used to evaluate the long-term toxicity of drugs or particles on the human bronchial epithelium, and subsequently to investigate their effect on the epithelial cell secretions.Daniel Sanchez-GuzmanSonja BolandOliver BrookesClaire Mc CordRené Lai KuenValentina SirriArmelle Baeza SquibanStéphanie DevineauNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel Sanchez-Guzman Sonja Boland Oliver Brookes Claire Mc Cord René Lai Kuen Valentina Sirri Armelle Baeza Squiban Stéphanie Devineau Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium
description	Abstract The human bronchial epithelium is the first line of defense against atmospheric particles, pollutants, and respiratory pathogens such as the novel SARS-CoV-2. The epithelial cells form a tight barrier and secrete proteins that are major components of the mucosal immune response. Functional in vitro models of the human lung are essential for screening the epithelial response and assessing the toxicity and barrier crossing of drugs, inhaled particles, and pollutants. However, there is a lack of models to investigate the effect of chronic exposure without resorting to animal testing. Here, we developed a 3D model of the human bronchial epithelium using Calu-3 cell line and demonstrated its viability and functionality for 21 days without subculturing. We investigated the effect of reduced Fetal Bovine Serum supplementation in the basal medium and defined the minimal supplementation needed to maintain a functional epithelium, so that the amount of exogenous serum proteins could be reduced during drug testing. The long-term evolution of the epithelial cell secretome was fully characterized by quantitative mass spectrometry in two preclinical models using Calu-3 or primary NHBE cells. 408 common secreted proteins were identified while significant differences in protein abundance were observed with time, suggesting that 7–10 days are necessary to establish a mature secretome in the Calu-3 model. The associated Reactome pathways highlight the role of the secreted proteins in the immune response of the bronchial epithelium. We suggest this preclinical 3D model can be used to evaluate the long-term toxicity of drugs or particles on the human bronchial epithelium, and subsequently to investigate their effect on the epithelial cell secretions.
format	article
author	Daniel Sanchez-Guzman Sonja Boland Oliver Brookes Claire Mc Cord René Lai Kuen Valentina Sirri Armelle Baeza Squiban Stéphanie Devineau
author_facet	Daniel Sanchez-Guzman Sonja Boland Oliver Brookes Claire Mc Cord René Lai Kuen Valentina Sirri Armelle Baeza Squiban Stéphanie Devineau
author_sort	Daniel Sanchez-Guzman
title	Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium
title_short	Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium
title_full	Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium
title_fullStr	Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium
title_full_unstemmed	Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium
title_sort	long-term evolution of the epithelial cell secretome in preclinical 3d models of the human bronchial epithelium
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8c85b49ef2a94a1ea94ba083387fcfe0
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Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium

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