The effect of stromal components on the modulation of the phenotype of human bronchial epithelial cells in 3D culture

The stroma plays an important role in the development and progression of human diseases. Pulmonary diseases such as asthma, fibrosis and cancer are thought to be the result of altered communications between the epithelial and stromal tissue compartments. In order to study these epithelial–mesenchyma...

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Bibliographic Details
Published in:Biomaterials Vol. 32; no. 29; pp. 7169 - 7180
Main Authors: Pageau, Steven C., Sazonova, Olga V., Wong, Joyce Y., Soto, Ana M., Sonnenschein, Carlos
Format: Journal Article
Language:English
Published: Netherlands Elsevier Ltd 01.10.2011
Subjects:
adults
Advanced Basic Science
Animals
apoptosis
asthma
biomechanics
Bronchi - cytology
Bronchi - pathology
Bronchi - physiology
Cell Culture Techniques
cell viability
Cells, Cultured
Co-culture
Coculture Techniques
Collagen
Collagen - metabolism
Connective Tissue - anatomy & histology
Connective Tissue - metabolism
Dentistry
ECM (extracellular matrix)
epithelial cells
Epithelial Cells - cytology
Epithelial Cells - physiology
epithelium
extracellular matrix
Extracellular Matrix - chemistry
Extracellular Matrix - metabolism
Fibroblast
fibroblasts
Fibroblasts - cytology
Fibroblasts - physiology
fibrosis
gels
Gene Expression
genes
human diseases
Humans
immune response
Lung
Lung Neoplasms - pathology
mitosis
Phenotype
Stromal Cells - cytology
Stromal Cells - physiology
ECM (extracellular matrix)
Co-culture
Fibroblast
Collagen
Lung
ISSN:0142-9612, 1878-5905, 1878-5905
Online Access:Get full text
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Summary:The stroma plays an important role in the development and progression of human diseases. Pulmonary diseases such as asthma, fibrosis and cancer are thought to be the result of altered communications between the epithelial and stromal tissue compartments. In order to study these epithelial–mesenchymal interactions, we developed a three dimensional (3D) in vitro model of the human airway that mimics bronchial morphology and function. This model consists of a type-I collagen matrix, normal human fetal lung fibroblasts (IMR-90) or primary human adult lung cancer-associated fibroblasts (LuCAFs), and a surface epithelium of normal human bronchial epithelial cells (HBECs). When cultured at an air–liquid interface (ALI), the epithelial component generated a well-differentiated pseudo-stratified bronchial epithelium that contained basal, ciliated, and non-ciliated (secretory) epithelial cells. IMR-90 and LuCAFs differentially altered the phenotype of HBECs in distinct ways. While IMR-90 permitted HBECs to form a typical respiratory surface epithelium, LuCAFs promoted HBECs to invade the collagen gel forming both epithelial nodules and cysts, suggesting that LuCAFs may alter the HBEC phenotype by modifying biomechanical signals conveyed through the extracellular matrix (ECM). Furthermore, LuCAFs secreted soluble factors that induced HBECs to express genes associated with immune responses, apoptosis, mitosis, cell survival, differentiation and cancer.
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ISSN:0142-9612
1878-5905
1878-5905
DOI:10.1016/j.biomaterials.2011.06.017