Tubule Formation and Functional Differentiation by Human Epithelial Respiratory Cells Cultured in a Three-Dimensional Collagen Matrix

Benali, Rachid; Chevillard, Martine; Zahm, Jean‐Marie; Hinnrasky, Jocelyne; Klossek, Jean‐Michel; Puchelle, Édith

doi:10.1378/chest.101.3_supplement.7s

Cited by 10 publications

(8 citation statements)

References 13 publications

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“…Tubules express MUC5B and lysozyme, but not acetylated a-tubulin or MUC5AC, and thus exhibited similar molecular, but not structural, characteristics with acini. A study in which human nasal polyp surface epithelial cells were grown on Col I for 13 days showed tubules with similar morphological structures to ours, with two different types of tubules observed by electron microscopy (20,21). In one type, there were numerous ciliated cells as well as preciliated cells that exhibit secretory granules and centrioles migrating toward the cell apex.…”

Section: Discussionsupporting

confidence: 79%

“…Matrigel also promotes the differentiation of HBE cells into glandular acini that express glandular markers (12). Col I promotes the organization of nasal polyp epithelial and HBE cells into tube-like structures (20,21). HBE cells cocultured with fetal lung fibroblasts on Col I form tubular structures that undergo dichotomous branching (22), implying that ECM and fibroblasts are associated with glandular development.…”

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confidence: 99%

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Development of Glandular Models from Human Nasal Progenitor Cells

Mimms

Banigan

et al. 2015

Am J Respir Cell Mol Biol

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Hyperplasia/hypertrophy of submucosal glands contributes to mucus overproduction in chronic diseases of the upper and lower respiratory tracts, especially in adult and pediatric chronic rhinosinusitis. Mechanisms that lead to glandular hyperplasia/ hypertrophy are markedly understudied, reflecting a lack of in vitro model systems wherein airway epithelial progenitor cells differentiate into glandular cells. In this study, we developed and compared several in vitro three-dimensional systems using human nasal epithelial basal cells (HNEBCs) cultured by different methods on two types of extracellular matrices. We demonstrate that HNEBCs cultured on Matrigel (Corning, Tewksbury, MA) form glandular acini-like structures, whereas HNEBCs embedded in a collagen type I matrix form a network of tubules. Fibroblast-conditioned medium increases tubule formation in collagen type I. In contrast, HNEBCs cocultured with fibroblasts self-aggregate into organotypic structures with tubules and acini. These observations provide morphological evidence that HNEBCs are pluripotent and retain the capacity to differentiate into structures resembling specific structural components of submucosal glands depending on the extracellular matrices and culture conditions. The resultant models should prove useful in targeting cross-talk between epithelial cells and fibroblasts to decipher molecular mechanisms and specific signals responsible for the development of glandular hyperplasia/hypertrophy, which in turn may lead to new therapeutic strategies for chronic rhinosinusitis and other inflammatory respiratory diseases characterized by glandular hyperplasia/hypertrophy.Keywords: human nasal epithelial cells; sinonasal basal cells; glandular hyperplasia/hypertrophy; extracellular matrix; chronic rhinosinusitis Clinical RelevanceThe resultant three-dimensional models should be useful for studying the development of sinonasal submucosal glands and submucosal glandular hyperplasia/hypertrophy in chronic rhinosinusitis and for deciphering the molecular mechanisms and specific signals responsible for sinonasal basal cell activation. This in turn would enable studies on how to reverse glandular hyperplasia, thereby decreasing mucin overproduction and morbidity in patients with chronic rhinosinusitis. This model may also be applicable to diseases of the lower respiratory tract that exhibit glandular hyperplasia.

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Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 99%

Development of Glandular Models from Human Nasal Progenitor Cells

Mimms

Banigan

et al. 2015

Am J Respir Cell Mol Biol

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“…The difficulty inherent in mechanically manipulating cultures on microporous substrates stems from the relatively inextensible nature of the substrates (113). One alternative is to grow the cells on gels of collagen type I (114)(115)(116)(117)(118)(119)(120)(121). Intriguingly, in addition to having effects on receptor ligation, the soft collagen gels influence the function and phenotype of cells (see below for further discussion of the possible mechanism), as opposed to rigid substrates or substrates coated with only a thin layer of collagen (116).…”

Section: The Airway Epitheliummentioning

confidence: 99%

“…Intriguingly, in addition to having effects on receptor ligation, the soft collagen gels influence the function and phenotype of cells (see below for further discussion of the possible mechanism), as opposed to rigid substrates or substrates coated with only a thin layer of collagen (116). Further changes are induced when the gels are cultivated in a manner that allows them to deform in response to the cells cultured on their surface (118,120,121); these changes suggest interesting parallels with the mechanical and developmental context of the rapidly proliferating epithelium and remodeling matrix present in the fetal lung (5,44). …”

Section: The Airway Epitheliummentioning

confidence: 99%

Chronic Effects of Mechanical Force on Airways

Tschumperlin¹,

Drazen²

2006

Annu. Rev. Physiol.

127

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Airways are embedded in the mechanically dynamic environment of the lung. In utero, this mechanical environment is defined largely by fluid secretion into the developing airway lumen. Clinical, whole lung, and cellular studies demonstrate pivotal roles for mechanical distention in airway morphogenesis and cellular behavior during lung development. In the adult lung, the mechanical environment is defined by a dynamic balance of surface, tissue, and muscle forces. Diseases of the airways modulate both the mechanical stresses to which the airways are exposed as well as the structure and mechanical behavior of the airways. For instance, in asthma, activation of airway smooth muscle abruptly changes the airway size and stress state within the airway wall; asthma also results in profound remodeling of the airway wall. Data now demonstrate that airway epithelial cells, smooth muscle cells, and fibroblasts respond to their mechanical environment. A prominent role has been identified for the epithelium in transducing mechanical stresses, and in both the fetal and mature airways, epithelial cells interact with mesenchymal cells to coordinate remodeling of tissue architecture in response to the mechanical environment.

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“…The ability of human adult nasal surface epithelial cells to form gland-like structures in a collagen gel has been recently demonstrated in vitro [25]. In vivo, the presence of glandular cell markers in surface epithelial cells of remodelled epithelia have already been described.…”

Section: Discussionmentioning

confidence: 96%

Identification of antileucoprotease in remodelled human adult nasal surface epithelium

Marchand

Tournier²,

Chevillard³

et al. 1995

Eur Respir J

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Antileucoprotease (ALP) is generally considered as a specific marker for glandular serous cells, and plays a major role in the defence of the respiratory tract against proteolytic damage. Nevertheless, several studies have identified ALP in bronchial and bronchiolar surface epithelial cells, and also an increased number of ALP-containing cells in bronchiolar tissue during the development of pulmonary diseases. In order to define more clearly whether the surface epithelium might be involved in the defence of the respiratory mucosa, we have investigated the expression of ALP by cells of the nasal surface epithelium.Indirect immunocytochemistry and in situ hybridization for ALP were performed on human nasal polyp sections. The height of the surface epithelium, its morphology, and the degree of local inflammation were assessed in parallel.Surface epithelium morphology was highly heterogeneous. ALP-containing cells were identified, but only in remodelled areas of the surface epithelium (foldings, basal cell and/or mucous cell hyperplasia), with no association to the degree of inflammation.These results demonstrate that the surface epithelial cells of the human adult nasal mucosa can express ALP in remodelled surface epithelium, and may be actively involved in the biochemical defence of the airways. Eur Respir J., 1995, 8, 15-21.

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Tubule Formation and Functional Differentiation by Human Epithelial Respiratory Cells Cultured in a Three-Dimensional Collagen Matrix

Cited by 10 publications

References 13 publications

Development of Glandular Models from Human Nasal Progenitor Cells

Development of Glandular Models from Human Nasal Progenitor Cells

Chronic Effects of Mechanical Force on Airways

Identification of antileucoprotease in remodelled human adult nasal surface epithelium

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