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

Autor:	Alberto Fucarino, Donna E. Davies, Massimo Cajozzo, Vito Marcianò, Roberto Marchese, Celeste Caruso Bavisotto, Antonella Marino Gammazza, Fabio Bucchieri, Giorgio Lo Iacono, Stephen T. Holgate, Giovanni Zummo, Alessandro Pitruzzella
Přispěvatelé:	Bucchieri F, Pitruzzella A, Fucarino A, Gammazza AM, Bavisotto CC, Marcianò V, Cajozzo M, Lo Iacono G, Marchese R, Zummo G, Holgate ST, Davies, DE
Rok vydání:	2017
Předmět:	0301 basic medicine Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Clinical Biochemistry Bronchi Respiratory Mucosa Biology Immunofluorescence Models Biological fibroblast bronchial 03 medical and health sciences In vivo Smoke medicine Humans Fibroblast Molecular Biology Cells Cultured Tissue homeostasis Microscopy Matrigel ECM electron microscopy medicine.diagnostic_test cigarette smoke Mesenchymal stem cell Epithelial Cells Mesenchymal Stem Cells Epithelium Cell biology Drug Combinations 030104 developmental biology medicine.anatomical_structure in vitro model Motile cilium Proteoglycans Collagen Laminin epithelium
Zdroj:	Experimental Lung Research. 43:82-92
ISSN:	1521-0499 0190-2148
Popis:	Background/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 of 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9bed2596cb7db1a36a00f24c3a932754 https://doi.org/10.1080/01902148.2017.1303098 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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