Isolation and Clonal Assay of Adult Lung Epithelial Stem/Progenitor Cells

Bertoncello, Ivan; McQualter, Jonathan L.

doi:10.1002/9780470151808.sc02g01s16

Cited by 31 publications

(38 citation statements)

References 14 publications

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“…Cell suspensions were isolated from whole lung or from the airways and parenchymal regions by dispase/collagenase tissue digestion (see Microdissection of conducting airways), and prepared for flow cytometry as described [13] with modifications. Briefly, cells were resuspended in PBS supplemented with 2% FBS on ice.…”

Section: Flow Cytometrymentioning

confidence: 99%

Behavioral Heterogeneity of Adult Mouse Lung Epithelial Progenitor Cells

Chernaya

Shinin²,

Liu³

et al. 2014

Stem Cells and Development

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The existence and identity of multipotent stem cells in the adult lung is currently highly debated. At present, it remains unclear whether candidate stem/progenitor cells are located in the airways, alveoli, or throughout the epithelial lining of the lung. Here, we introduce a method of airway microdissection, which enabled us to study the progenitor behavior of pulmonary epithelial cells in region-specific contexts. The progenitor characteristics of epithelial cells isolated from the trachea, proximal and distal airways, and lung parenchyme were evaluated in vitro and in vivo. We identified a population of airway-derived basal-like epithelial cells with the potential to self-renew and differentiate into airway and alveolar lineages in culture and in vivo after subcutaneous transplantation. The multipotent candidate progenitors originated from a minor fraction of the airway epithelial cell population characterized by high expression of a6 integrin. Results of the current study provide new insights into the regenerative potential of region-specific integrin a6-positive pulmonary epithelial cells.

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Section: Flow Cytometrymentioning

confidence: 99%

Behavioral Heterogeneity of Adult Mouse Lung Epithelial Progenitor Cells

Chernaya

Shinin²,

Liu³

et al. 2014

Stem Cells and Development

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“…Recently, an in vitro study has described the formation of bronchospheres and tracheospheres differentiated from isolated murine and human tracheal BCs (33,34). In contrast to the acinar and tubular structures, bronchospheres/tracheospheres have ciliated cells lining a hollow lumen that lacks detectable secretory cells (33,34).…”

Section: Discussionmentioning

confidence: 99%

“…The data further support the emerging paradigm that the similar characteristics of upper and lower airway epithelium reflect the similarity of their progenitor BCs. Only recently has it been demonstrated that HBEBCs differentiate into a conducting airway epithelium (8) or bronchospheres (33,34), although it is well recognized that HBE cells differentiate into a conducting airway epithelium when grown on Tranwells under ALI conditions (9)(10)(11) or into glandular acinar structures when grown on Matrigel (12).…”

Section: Discussionmentioning

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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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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“…Therapies that could utilize cells with the capacity to remodel damaged parenchyma would represent a major advance in treating such patients. Although cell based therapies are not yet available, significant progress has been made in the past few years identifying putative reparative cells that may one day have therapeutic application [1][2][3][4][5][6][7]. Emerging data shows that stem and progenitor cells exist in the distal airspaces that have the capacity to differentiate into alveolar epithelial type II (AECII) and type I (AECI) cells.…”

Section: Introductionmentioning

confidence: 98%

Alveolar Epithelial Stem and Progenitor Cells: Emerging Evidence for their Role in Lung Regeneration

Hoffman

Ingenito²

2012

Current Medicinal Chemistry

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Lung injuries that impact the alveolus, such as emphysema, pulmonary fibrosis, and acute lung injury, are costly and prevalent problems. Moreover, the extent of alveolar injury and impairment of gas exchange is strongly associated with prognosis and survival. Thus, mechanisms of repair and regeneration of the lung alveolar compartment have received mounting attention as newer approaches to the study of stem and progenitor cells in this region unfold. The role of type II alveolar epithelial as the sole source of type I (AECI) and II (AECII) alveolar epithelial cells following lung injury has been recently challenged; recently, investigators have described stemprogenitor cells that function like precursors to AECII either in vitro or in vivo, both in mice and humans. Techniques to explore selfrenewal and multipotency have been rigorously applied to these putative stem-progenitor cell populations and the data thus far is compelling. This review provides background to the study of alveolar regeneration with the aim to provide context to the recent discoveries of putative stem-progenitor cells that may contribute to this process.

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Isolation and Clonal Assay of Adult Lung Epithelial Stem/Progenitor Cells

Cited by 31 publications

References 14 publications

Behavioral Heterogeneity of Adult Mouse Lung Epithelial Progenitor Cells

Behavioral Heterogeneity of Adult Mouse Lung Epithelial Progenitor Cells

Development of Glandular Models from Human Nasal Progenitor Cells

Alveolar Epithelial Stem and Progenitor Cells: Emerging Evidence for their Role in Lung Regeneration

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