title: Development of glandular models from human nasal progenitor cells.
abstract: 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.
authors.affiliation: 1 Center for Genetic Medicine Research and.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wu
authors.forename: Remy
authors.initials: R
authors.lastname: Mimms
authors.forename: Maureen
authors.initials: M
authors.lastname: Banigan
authors.forename: Michael
authors.initials: M
authors.lastname: Lee
authors.forename: Viktoria
authors.initials: V
authors.lastname: Elkis
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Peters-Hall
authors.forename: Humaira
authors.initials: H
authors.lastname: Mubeen
authors.forename: Andrew
authors.initials: A
authors.lastname: Joselow
authors.forename: Maria T
authors.initials: MT
authors.lastname: Peña
authors.forename: Mary C
authors.initials: MC
authors.lastname: Rose
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D004338:Drug Combinations; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D005088:Exocrine Glands / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005782:Gels; D006801:Humans; D007797:Laminin / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D038081:Organogenesis; D019899:Paracrine Communication; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D055153:Stem Cell Niche; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D024042:Collagen Type I; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D005782:Gels; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen
keywords: chronic rhinosinusitis; extracellular matrix; glandular hyperplasia/hypertrophy; human nasal epithelial cells; sinonasal basal cells