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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Vydané v:	Biomaterials Ročník 32; číslo 29; s. 7169 - 7180
Hlavní autori:	Pageau, Steven C., Sazonova, Olga V., Wong, Joyce Y., Soto, Ana M., Sonnenschein, Carlos
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Netherlands Elsevier Ltd 01.10.2011
Predmet:	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
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Abstract	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.
AbstractList	Abstract 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. 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. 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.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. 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.
Author	Wong, Joyce Y. Sonnenschein, Carlos Pageau, Steven C. Sazonova, Olga V. Soto, Ana M.
Author_xml	– sequence: 1 givenname: Steven C. surname: Pageau fullname: Pageau, Steven C. organization: Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA – sequence: 2 givenname: Olga V. surname: Sazonova fullname: Sazonova, Olga V. organization: Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA – sequence: 3 givenname: Joyce Y. surname: Wong fullname: Wong, Joyce Y. organization: Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA – sequence: 4 givenname: Ana M. surname: Soto fullname: Soto, Ana M. organization: Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA – sequence: 5 givenname: Carlos surname: Sonnenschein fullname: Sonnenschein, Carlos email: carlos.sonnenschein@tufts.edu organization: Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA
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Keywords	ECM (extracellular matrix) Co-culture Fibroblast Collagen Lung
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Snippet	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... Abstract The stroma plays an important role in the development and progression of human diseases. Pulmonary diseases such as asthma, fibrosis and cancer are...
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SubjectTerms	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
Title	The effect of stromal components on the modulation of the phenotype of human bronchial epithelial cells in 3D culture
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