Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit

Alberto Giuseppe Fucarino, Alessandro Pitruzzella, Giovanni Zummo, Massimo Cajozzo, Celeste Caruso Bavisotto, Fabio Bucchieri, Antonella Marino Gammazza, Alessandro Pitruzzella, Alberto Fucarino, Celeste Caruso Bavisotto, Fabio Bucchieri, Stephen T. Holgate, Donna E. Davies, Roberto Marchese, Vito Marciano'

Risultato della ricerca: Article

7 Citazioni (Scopus)

Abstract

AbstractBACKGROUND/AIM:Epithelial-mesenchymal communication plays a key role in tissue homeostasis and abnormal signaling contributes to chronic airways disease such as COPD. Most in vitro models are limited in complexity and poorly represent this epithelial-mesenchymal trophic unit. We postulated that cellular outgrowth from bronchial tissue would enable development of a mucosal structure that recapitulates better in vivo tissue architecture.MATERIALS AND METHODS:Bronchial tissue was embedded in Matrigel and outgrowth cultures monitored using time-lapse microscopy, electrical resistance, light and electron microscopy. Cultures were challenged repetitively with cigarette smoke extract (CSE).RESULTS:The outgrowths formed as a multicellular sheet with motile cilia becoming evident as the Matrigel was remodeled to provide an air interface; cultures were viable for more than one year. Immunofluorescence and electron microscopy (EM) identified an upper layer of mucociliary epithelium and a lower layer of highly organized extracellular matrix (ECM) interspersed with fibroblastic cells separated by a basement membrane. EM analysis of the mucosal construct after repetitive exposure to CSE revealed epithelial damage, loss of cilia, and ECM remodeling, as occurs in vivo.CONCLUSIONS:We have developed a robust bronchial mucosal model. The structural changes observed following CSE exposure suggest the model should have utility for drug discovery and preclinical testing, especially those targeting airway remodeling.
Lingua originaleEnglish
pagine (da-a)82-92
Numero di pagine11
RivistaDefault journal
Volume43
Stato di pubblicazionePublished - 2017

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Smoke
Tobacco Products
Electron microscopy
Tissue
Electron Microscopy
Cilia
Tissue homeostasis
Extracellular Matrix
Acoustic impedance
Airway Remodeling
Optical microscopy
Microscopic examination
Drug Discovery
Electric Impedance
Fluorescence Microscopy
Basement Membrane
Chronic Obstructive Pulmonary Disease
Microscopy
Homeostasis
Chronic Disease

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit. / Fucarino, Alberto Giuseppe; Pitruzzella, Alessandro; Zummo, Giovanni; Cajozzo, Massimo; Caruso Bavisotto, Celeste; Bucchieri, Fabio; Gammazza, Antonella Marino; Pitruzzella, Alessandro; Fucarino, Alberto; Bavisotto, Celeste Caruso; Bucchieri, Fabio; Holgate, Stephen T.; Davies, Donna E.; Marchese, Roberto; Marciano', Vito.

In: Default journal, Vol. 43, 2017, pag. 82-92.

Risultato della ricerca: Article

Fucarino, AG, Pitruzzella, A, Zummo, G, Cajozzo, M, Caruso Bavisotto, C, Bucchieri, F, Gammazza, AM, Pitruzzella, A, Fucarino, A, Bavisotto, CC, Bucchieri, F, Holgate, ST, Davies, DE, Marchese, R & Marciano', V 2017, 'Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit', Default journal, vol. 43, pagg. 82-92.
Fucarino, Alberto Giuseppe ; Pitruzzella, Alessandro ; Zummo, Giovanni ; Cajozzo, Massimo ; Caruso Bavisotto, Celeste ; Bucchieri, Fabio ; Gammazza, Antonella Marino ; Pitruzzella, Alessandro ; Fucarino, Alberto ; Bavisotto, Celeste Caruso ; Bucchieri, Fabio ; Holgate, Stephen T. ; Davies, Donna E. ; Marchese, Roberto ; Marciano', Vito. / Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit. In: Default journal. 2017 ; Vol. 43. pagg. 82-92.
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abstract = "AbstractBACKGROUND/AIM:Epithelial-mesenchymal communication plays a key role in tissue homeostasis and abnormal signaling contributes to chronic airways disease such as COPD. Most in vitro models are limited in complexity and poorly represent this epithelial-mesenchymal trophic unit. We postulated that cellular outgrowth from bronchial tissue would enable development of a mucosal structure that recapitulates better in vivo tissue architecture.MATERIALS AND METHODS:Bronchial tissue was embedded in Matrigel and outgrowth cultures monitored using time-lapse microscopy, electrical resistance, light and electron microscopy. Cultures were challenged repetitively with cigarette smoke extract (CSE).RESULTS:The outgrowths formed as a multicellular sheet with motile cilia becoming evident as the Matrigel was remodeled to provide an air interface; cultures were viable for more than one year. Immunofluorescence and electron microscopy (EM) identified an upper layer of mucociliary epithelium and a lower layer of highly organized extracellular matrix (ECM) interspersed with fibroblastic cells separated by a basement membrane. EM analysis of the mucosal construct after repetitive exposure to CSE revealed epithelial damage, loss of cilia, and ECM remodeling, as occurs in vivo.CONCLUSIONS:We have developed a robust bronchial mucosal model. The structural changes observed following CSE exposure suggest the model should have utility for drug discovery and preclinical testing, especially those targeting airway remodeling.",
author = "Fucarino, {Alberto Giuseppe} and Alessandro Pitruzzella and Giovanni Zummo and Massimo Cajozzo and {Caruso Bavisotto}, Celeste and Fabio Bucchieri and Gammazza, {Antonella Marino} and Alessandro Pitruzzella and Alberto Fucarino and Bavisotto, {Celeste Caruso} and Fabio Bucchieri and Holgate, {Stephen T.} and Davies, {Donna E.} and Roberto Marchese and Vito Marciano'",
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T1 - Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit

AU - Fucarino, Alberto Giuseppe

AU - Pitruzzella, Alessandro

AU - Zummo, Giovanni

AU - Cajozzo, Massimo

AU - Caruso Bavisotto, Celeste

AU - Bucchieri, Fabio

AU - Gammazza, Antonella Marino

AU - Pitruzzella, Alessandro

AU - Fucarino, Alberto

AU - Bavisotto, Celeste Caruso

AU - Bucchieri, Fabio

AU - Holgate, Stephen T.

AU - Davies, Donna E.

AU - Marchese, Roberto

AU - Marciano', Vito

PY - 2017

Y1 - 2017

N2 - AbstractBACKGROUND/AIM:Epithelial-mesenchymal communication plays a key role in tissue homeostasis and abnormal signaling contributes to chronic airways disease such as COPD. Most in vitro models are limited in complexity and poorly represent this epithelial-mesenchymal trophic unit. We postulated that cellular outgrowth from bronchial tissue would enable development of a mucosal structure that recapitulates better in vivo tissue architecture.MATERIALS AND METHODS:Bronchial tissue was embedded in Matrigel and outgrowth cultures monitored using time-lapse microscopy, electrical resistance, light and electron microscopy. Cultures were challenged repetitively with cigarette smoke extract (CSE).RESULTS:The outgrowths formed as a multicellular sheet with motile cilia becoming evident as the Matrigel was remodeled to provide an air interface; cultures were viable for more than one year. Immunofluorescence and electron microscopy (EM) identified an upper layer of mucociliary epithelium and a lower layer of highly organized extracellular matrix (ECM) interspersed with fibroblastic cells separated by a basement membrane. EM analysis of the mucosal construct after repetitive exposure to CSE revealed epithelial damage, loss of cilia, and ECM remodeling, as occurs in vivo.CONCLUSIONS:We have developed a robust bronchial mucosal model. The structural changes observed following CSE exposure suggest the model should have utility for drug discovery and preclinical testing, especially those targeting airway remodeling.

AB - AbstractBACKGROUND/AIM:Epithelial-mesenchymal communication plays a key role in tissue homeostasis and abnormal signaling contributes to chronic airways disease such as COPD. Most in vitro models are limited in complexity and poorly represent this epithelial-mesenchymal trophic unit. We postulated that cellular outgrowth from bronchial tissue would enable development of a mucosal structure that recapitulates better in vivo tissue architecture.MATERIALS AND METHODS:Bronchial tissue was embedded in Matrigel and outgrowth cultures monitored using time-lapse microscopy, electrical resistance, light and electron microscopy. Cultures were challenged repetitively with cigarette smoke extract (CSE).RESULTS:The outgrowths formed as a multicellular sheet with motile cilia becoming evident as the Matrigel was remodeled to provide an air interface; cultures were viable for more than one year. Immunofluorescence and electron microscopy (EM) identified an upper layer of mucociliary epithelium and a lower layer of highly organized extracellular matrix (ECM) interspersed with fibroblastic cells separated by a basement membrane. EM analysis of the mucosal construct after repetitive exposure to CSE revealed epithelial damage, loss of cilia, and ECM remodeling, as occurs in vivo.CONCLUSIONS:We have developed a robust bronchial mucosal model. The structural changes observed following CSE exposure suggest the model should have utility for drug discovery and preclinical testing, especially those targeting airway remodeling.

UR - http://hdl.handle.net/10447/230055

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