Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit.
Exp Lung Res
; 43(2): 82-92, 2017 03.
Article
en En
| MEDLINE
| ID: mdl-28368678
ABSTRACT
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 ANDMETHODS:
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Humo
/
Modelos Biológicos
Límite:
Humans
Idioma:
En
Revista:
Exp Lung Res
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido