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  1. Article ; Online: Endogenous lung stem cells for lung regeneration.

    McQualter, Jonathan L

    Expert opinion on biological therapy

    2019  Volume 19, Issue 6, Page(s) 539–546

    Abstract: Introduction: Lifelong maintenance of a healthy lung requires resident stem cells to proliferate according to tissue requirements. Once thought to be a quiescent tissue, evolving views of the complex differentiation landscape of lung stem and progenitor ...

    Abstract Introduction: Lifelong maintenance of a healthy lung requires resident stem cells to proliferate according to tissue requirements. Once thought to be a quiescent tissue, evolving views of the complex differentiation landscape of lung stem and progenitor cells have broad implications for our understanding of how the lung is maintained, as well as the development of new therapies for promoting endogenous regeneration in lung disease.
    Areas covered: This review collates a large body of research relating to the hierarchical organization of epithelial stem cells in the adult lung and their role in tissue homeostasis and regeneration after injury. To identify relevant studies, PubMed was queried using one or a combination of the terms 'lung', 'airway', 'alveoli', 'stem cells', 'progenitor', 'repair' and 'regeneration'.
    Expert opinion: This review discusses how new technologies and injury models have challenged the demarcations between stem and progenitor cell populations.
    MeSH term(s) Animals ; Cell Differentiation ; Humans ; Lung/physiology ; Lung Diseases/therapy ; Pulmonary Alveoli/cytology ; Regeneration ; Stem Cell Transplantation ; Stem Cells/cytology ; Stem Cells/metabolism
    Language English
    Publishing date 2019-03-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2052501-1
    ISSN 1744-7682 ; 1471-2598
    ISSN (online) 1744-7682
    ISSN 1471-2598
    DOI 10.1080/14712598.2019.1596256
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    Zs.A 6094: Show issues Location:
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  2. Article ; Online: Enhanced Lyn Activity Causes Severe, Progressive Emphysema and Lung Cancer.

    Tsantikos, Evelyn / Gottschalk, Timothy A / L'Estrange-Stranieri, Elan / O'Brien, Caitlin A / Raftery, April L / Wickramasinghe, Lakshanie C / McQualter, Jonathan L / Anderson, Gary P / Hibbs, Margaret L

    American journal of respiratory cell and molecular biology

    2023  Volume 69, Issue 1, Page(s) 99–112

    Abstract: The epidemiological patterns of incident chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma are changing, with an increasing fraction of disease occurring in patients who are never-smokers or were not exposed to traditional risk factors. ...

    Abstract The epidemiological patterns of incident chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma are changing, with an increasing fraction of disease occurring in patients who are never-smokers or were not exposed to traditional risk factors. However, causative mechanism(s) are obscure. Overactivity of Src family kinases (SFKs) and myeloid cell-dependent inflammatory lung epithelial and endothelial damage are independent candidate mechanisms, but their pathogenic convergence has not been demonstrated. Here we present a novel preclinical model in which an activating mutation in Lyn, a nonreceptor SFK that is expressed in immune cells, epithelium, and endothelium-all strongly implicated in the pathogenesis of COPD-causes spontaneous inflammation, early-onset progressive emphysema, and lung adenocarcinoma. Surprisingly, even though activated macrophages, elastolytic enzymes, and proinflammatory cytokines were prominent, bone marrow chimeras formally demonstrated that myeloid cells were not disease initiators. Rather, lung disease arose from aberrant epithelial cell proliferation and differentiation, microvascular lesions within an activated endothelial microcirculation, and amplified EGFR (epidermal growth factor receptor) expression. In human bioinformatics analyses,
    MeSH term(s) Humans ; Adenocarcinoma of Lung/genetics ; Emphysema ; ErbB Receptors/metabolism ; Lung Neoplasms/genetics ; Pulmonary Disease, Chronic Obstructive/metabolism ; Pulmonary Emphysema/genetics ; src-Family Kinases/metabolism
    Chemical Substances ErbB Receptors (EC 2.7.10.1) ; src-Family Kinases (EC 2.7.10.2) ; lyn protein-tyrosine kinase (EC 2.7.10.2)
    Language English
    Publishing date 2023-04-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2022-0463OC
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    Zs.A 2851: Show issues Location:
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  3. Article ; Online: Detection, Labeling, and Culture of Lung Stem and Progenitor Cells.

    Bertoncello, Ivan / Carraro, Gianni / McQualter, Jonathan L

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1842, Page(s) 167–181

    Abstract: Identification, isolation, and clonal culture of stem cells is essential for understanding their proliferative and differentiation potential, and the cellular and molecular mechanisms that regulate their fate. Akin to development in vivo, the in vitro ... ...

    Abstract Identification, isolation, and clonal culture of stem cells is essential for understanding their proliferative and differentiation potential, and the cellular and molecular mechanisms that regulate their fate. Akin to development in vivo, the in vitro growth of adult lung epithelial stem cells requires support of mesenchymal-derived growth factors. In the adult mouse lung, epithelial stem/progenitor cells are defined by the phenotype CD45neg CD31neg EpCAMpos CD104pos CD24low, and mesenchymal cells are defined by the phenotype CD45neg CD31neg EpCAMneg Sca-1hi. Here we describe a method for primary cell isolation from the adult mouse lung, a flow cytometry strategy for fractionation of epithelial stem/progenitor cells and mesenchymal cells, and a three-dimensional epithelial colony-forming assay.
    MeSH term(s) Adult Stem Cells/cytology ; Adult Stem Cells/metabolism ; Animals ; Biomarkers ; Cell Culture Techniques ; Colony-Forming Units Assay ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Humans ; Immunophenotyping ; Lung/cytology ; Mice ; Phenotype ; Respiratory Mucosa/cytology
    Chemical Substances Biomarkers
    Language English
    Publishing date 2018-09-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-8697-2_11
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Delineating the hierarchy of lung progenitor cells and their response to influenza.

    McQualter, Jonathan L / Laurent, Geoffrey J

    The European respiratory journal

    2015  Volume 46, Issue 2, Page(s) 315–317

    MeSH term(s) Animals ; Epithelial Cells/cytology ; Epithelial Cells/pathology ; Female ; Humans ; Lung/cytology ; Lung/pathology ; Lung Injury/pathology ; Male ; Re-Epithelialization ; Stem Cells/cytology
    Language English
    Publishing date 2015-08
    Publishing country England
    Document type Comment ; Editorial
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/09031936.00011915
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2322: Show issues Location:
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    Zs.MO 292: Show issues

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  5. Article ; Online: Clonal culture of adult mouse lung epithelial stem/progenitor cells.

    McQualter, Jonathan L / Bertoncello, Ivan

    Methods in molecular biology (Clifton, N.J.)

    2015  Volume 1235, Page(s) 231–241

    Abstract: Clonal culture of stem cells is crucial for their identification, and the characterization of the cellular and molecular mechanisms that regulate their proliferation and differentiation. In the adult mouse lung, epithelial stem/progenitor cells are ... ...

    Abstract Clonal culture of stem cells is crucial for their identification, and the characterization of the cellular and molecular mechanisms that regulate their proliferation and differentiation. In the adult mouse lung, epithelial stem/progenitor cells are defined by the phenotype CD45(neg) CD31(neg) EpCAM(pos) CD104(pos) CD24(low). Here we describe a tissue dissociation and flow cytometry strategy for the detection and isolation of adult mouse lung epithelial stem/progenitor cells, and a three-dimensional colony-forming assay for their clonal culture in vitro.
    MeSH term(s) Adult Stem Cells/cytology ; Animals ; Antigens, Neoplasm/analysis ; CD24 Antigen/analysis ; Cell Adhesion Molecules/analysis ; Cell Culture Techniques/methods ; Cell Proliferation ; Cell Separation/methods ; Cells, Cultured ; Colony-Forming Units Assay/methods ; Epithelial Cell Adhesion Molecule ; Epithelial Cells/cytology ; Flow Cytometry/methods ; Integrin beta4/analysis ; Leukocyte Common Antigens/analysis ; Lung/cytology ; Mice ; Platelet Endothelial Cell Adhesion Molecule-1/analysis
    Chemical Substances Antigens, Neoplasm ; CD24 Antigen ; Cell Adhesion Molecules ; Epithelial Cell Adhesion Molecule ; Integrin beta4 ; Platelet Endothelial Cell Adhesion Molecule-1 ; Leukocyte Common Antigens (EC 3.1.3.48)
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-1785-3_17
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  6. Article ; Online: Lung stem cells: do they exist?

    Bertoncello, Ivan / McQualter, Jonathan L

    Respirology (Carlton, Vic.)

    2013  Volume 18, Issue 4, Page(s) 587–595

    Abstract: Recognition of the potential of stem cell-based therapies for alleviating intractable lung diseases has provided the impetus for research aimed at identifying regenerative cells in the adult lung, understanding how they are organized and regulated, and ... ...

    Abstract Recognition of the potential of stem cell-based therapies for alleviating intractable lung diseases has provided the impetus for research aimed at identifying regenerative cells in the adult lung, understanding how they are organized and regulated, and how they could be harnessed in lung regenerative medicine. In this review, we describe the attributes of adult stem and progenitor cells in adult organs and how they are regulated by the permissive or restrictive microenvironment in which they reside. We describe the power and limitations of experimental models, cell separative strategies and functional assays used to model the organization and regulation of adult airway and alveolar stem cells in the adult lung. The review summarizes recent progress and obstacles in defining endogenous lung epithelial stem and progenitor cells in mouse models and in translational studies.
    MeSH term(s) Adult Stem Cells/cytology ; Adult Stem Cells/transplantation ; Animals ; Cell- and Tissue-Based Therapy ; Disease Models, Animal ; Humans ; Lung/cytology ; Lung/physiology ; Lung Diseases/therapy ; Mice ; Regeneration/physiology ; Stem Cell Transplantation ; Stem Cells/cytology
    Language English
    Publishing date 2013-05
    Publishing country Australia
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1435849-9
    ISSN 1440-1843 ; 1323-7799
    ISSN (online) 1440-1843
    ISSN 1323-7799
    DOI 10.1111/resp.12073
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4957: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  7. Article ; Online: Concise review: Deconstructing the lung to reveal its regenerative potential.

    McQualter, Jonathan L / Bertoncello, Ivan

    Stem cells (Dayton, Ohio)

    2012  Volume 30, Issue 5, Page(s) 811–816

    Abstract: Despite burgeoning interest in the potential of cellular therapies in lung regenerative medicine, progress in delivering these therapies has been confounded by a lack of knowledge about the identity of appropriate targets which can be harnessed to repair ...

    Abstract Despite burgeoning interest in the potential of cellular therapies in lung regenerative medicine, progress in delivering these therapies has been confounded by a lack of knowledge about the identity of appropriate targets which can be harnessed to repair the lung, and the cellular and molecular factors which regulate their regenerative potential. While systematic analysis of lung development and cell lineage tracing studies in normal and perturbed animal models provides a framework for understanding the complex interplay of the multiple cell types, biomatrix elements and soluble and insoluble cytokines and factors that regulate lung structure and function, a reductionist approach is also required to analyze the organization of regenerative cells in the adult lung and identify the factors and molecular pathways which regulate their capacity to generate descendent lineages. In this review we describe recent progress in identifying and characterizing endogenous epithelial, mesenchymal and endothelial stem/progenitor cells in the adult lung using multiparameter cell separative strategies and functional in vitro clonogenic assays.
    MeSH term(s) Adult ; Adult Stem Cells/cytology ; Adult Stem Cells/metabolism ; Animals ; Cell Lineage/physiology ; Cytokines/metabolism ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Extracellular Matrix/metabolism ; Humans ; Lung/cytology ; Lung/embryology ; Lung/metabolism ; Mesenchymal Stromal Cells ; Mice ; Regenerative Medicine/methods
    Chemical Substances Cytokines
    Language English
    Publishing date 2012-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1143556-2
    ISSN 1549-4918 ; 1066-5099
    ISSN (online) 1549-4918
    ISSN 1066-5099
    DOI 10.1002/stem.1055
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    Zs.A 1894: Show issues Location:
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  8. Article ; Online: LysoTracker is a marker of differentiated alveolar type II cells.

    Van der Velden, Joanne L / Bertoncello, Ivan / McQualter, Jonathan L

    Respiratory research

    2013  Volume 14, Page(s) 123

    Abstract: Background: LysoTracker Green DND-26 is a fluorescent dye that stains acidic compartments in live cells and has been shown to selectively accumulate in lamellar bodies in alveolar type II (AT2) cells in the lung. The aim of this study was to determine ... ...

    Abstract Background: LysoTracker Green DND-26 is a fluorescent dye that stains acidic compartments in live cells and has been shown to selectively accumulate in lamellar bodies in alveolar type II (AT2) cells in the lung. The aim of this study was to determine whether the accumulation of LysoTracker in lamellar bodies can be used to isolate viable AT2 cells by flow cytometry and track their differentiation in live-cell culture by microscopy.
    Methods: Mouse lung cells were sorted on the basis of CD45(neg)CD31(neg)EpCAM(pos)LysoTracker(pos) expression and characterized by immunostaining for SP-C and cultured in a three-dimensional epithelial colony-forming unit (CFU-Epi) assay. To track AT2 cell differentiation, lung epithelial stem and progenitor cells were cultured in a CFU-Epi assay with LysoTracker-supplemented media.
    Results: The purity of sorted AT2 cells as determined by SP-C staining was 97.4% and viability was 85.3%. LysoTracker(pos) AT2 cells generated SP-C(pos) alveolar epithelial cell colonies in culture, and when added to the CFU-Epi culture medium, LysoTracker marked the differentiation of stem/progenitor-derived AT2 cells.
    Conclusions: This study describes a novel method for isolating AT2 cells from mouse lungs. The high purity and viability of cells attained by this method, makes them suitable for functional analysis in vitro. The application of LysoTracker to live cell cultures will allow better assessment of the cellular and molecular mechanisms that regulate AT2 cell differentiation.
    MeSH term(s) Amines ; Animals ; Cell Differentiation ; Cell Survival ; Cells, Cultured ; Female ; Flow Cytometry/methods ; Fluorescent Dyes ; In Vitro Techniques ; Lung/cytology ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Pulmonary Alveoli/cytology
    Chemical Substances Amines ; Fluorescent Dyes ; Red DND-99
    Language English
    Publishing date 2013-11-11
    Publishing country England
    Document type Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041675-1
    ISSN 1465-993X ; 1465-9921
    ISSN (online) 1465-993X
    ISSN 1465-9921
    DOI 10.1186/1465-9921-14-123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Endogenous lung stem cells: what is their potential for use in regenerative medicine?

    Bertoncello, Ivan / McQualter, Jonathan L

    Expert review of respiratory medicine

    2010  Volume 4, Issue 3, Page(s) 349–362

    Abstract: Advances in stem cell technologies in recent years have generated considerable interest in harnessing the potential of adult and embryonic stem cells in regenerative medicine. Stem cell-based therapies are a particularly attractive option for the ... ...

    Abstract Advances in stem cell technologies in recent years have generated considerable interest in harnessing the potential of adult and embryonic stem cells in regenerative medicine. Stem cell-based therapies are a particularly attractive option for the treatment of intractable lung diseases for which current therapies are essentially palliative. Proof-of-principle experiments in animal models demonstrate the efficacy of exogenous stem cells in mediating lung repair by attenuating fibrotic responses to injury, but also suggest that their ability to contribute to lung epithelial regeneration and repair is limited. Consequently, attention has turned to endogenous lung stem cells as targets or vehicles for the delivery of lung regenerative therapies. In this article, we discuss the potential and promise of endogenous lung stem cells in regenerative medicine, and the problems and challenges faced by researchers and clinicians in harnessing their potential to repair the lung.
    MeSH term(s) Adult ; Adult Stem Cells/physiology ; Adult Stem Cells/transplantation ; Animals ; Biomarkers/metabolism ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Cell Separation ; Humans ; Lung/pathology ; Lung/physiopathology ; Lung/surgery ; Lung Diseases/pathology ; Lung Diseases/physiopathology ; Lung Diseases/surgery ; Phenotype ; Regeneration ; Regenerative Medicine/methods ; Stem Cell Transplantation ; Transplantation, Autologous
    Chemical Substances Biomarkers
    Keywords covid19
    Language English
    Publishing date 2010-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2479146-5
    ISSN 1747-6356 ; 1747-6348
    ISSN (online) 1747-6356
    ISSN 1747-6348
    DOI 10.1586/ers.10.21
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    Zs.A 6963: Show issues Location:
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  10. Article ; Online: Single-Cell Reconstruction of Human Basal Cell Diversity in Normal and Idiopathic Pulmonary Fibrosis Lungs.

    Carraro, Gianni / Mulay, Apoorva / Yao, Changfu / Mizuno, Takako / Konda, Bindu / Petrov, Martin / Lafkas, Daniel / Arron, Joe R / Hogaboam, Cory M / Chen, Peter / Jiang, Dianhua / Noble, Paul W / Randell, Scott H / McQualter, Jonathan L / Stripp, Barry R

    American journal of respiratory and critical care medicine

    2020  Volume 202, Issue 11, Page(s) 1540–1550

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Aged ; Alveolar Epithelial Cells/cytology ; Alveolar Epithelial Cells/metabolism ; Basement Membrane ; Case-Control Studies ; Cell Plasticity ; Cell Proliferation/genetics ; Cell Self Renewal/genetics ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Female ; Gene Expression Profiling ; Humans ; Idiopathic Pulmonary Fibrosis/genetics ; Idiopathic Pulmonary Fibrosis/metabolism ; Male ; Middle Aged ; RNA-Seq ; Respiratory Mucosa/cytology ; Respiratory Mucosa/metabolism ; Single-Cell Analysis ; Transcriptome ; Young Adult
    Language English
    Publishing date 2020-07-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.201904-0792OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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