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

Alberto Giuseppe Fucarino, Alessandro Pitruzzella, Massimo Cajozzo, Giovanni Zummo, 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'

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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
RivistaExperimental Lung Research
Stato di pubblicazionePublished - 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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    Fucarino, A. G., Pitruzzella, A., Cajozzo, M., Zummo, G., Caruso Bavisotto, C., Bucchieri, F., Gammazza, A. M., Pitruzzella, A., Fucarino, A., Bavisotto, C. C., Bucchieri, F., Holgate, S. T., Davies, D. E., Marchese, R., & Marciano', V. (2017). Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit. Experimental Lung Research, 43, 82-92.