title: Harnessing the potential of lung stem cells for regenerative medicine.
abstract: In response to recurrent exposure to environmental insults such as allergens, pollution, irritants, smoke and viral/bacterial infection, the epithelium of the lung is continually damaged. Homeostasis of the lung requires a balance between immune regulation and promotion of tissue regeneration, which requires the co-ordinated proliferation and differentiation of stem and progenitor cells. In this review we reflect on the current understanding of lung epithelial stem and progenitor cells and advocate a model hierarchy in which self-renewing multipotent lung epithelial stem cells give rise to lineage restricted progenitor cells that repopulate airway and alveolar epithelial cell lineages during homeostasis and repair. We also discuss the role of mesenchymal progenitor cells in maintaining the structural integrity of the lung and propose a model in which mesenchymal cells act as the quintessential architects of lung regeneration by providing molecular signals, such as FGF-10, to regulate the fate and specificity of epithelial stem and progenitor cells. Moreover, we discuss the current status and future prospects for translating lung stem cell therapies to the clinic to replace, repair, or regenerate diseased lung tissue. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation.
authors.affiliation: Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Vic, Australia. Electronic address: jlmcq@unimelb.edu.au.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: McQualter
authors.affiliation: Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Vic, Australia.
authors.forename: Desiree
authors.initials: D
authors.lastname: Anthony
authors.affiliation: Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Vic, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Bozinovski
authors.affiliation: Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Perth, WA, Australia; Lung Institute of Western Australia and Centre for Asthma Allergy and Respiratory Research, School of Medicine and Pharmacology, The University of Western Australia, Perth, WA, Australia.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Prêle
authors.affiliation: Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Perth, WA, Australia; Lung Institute of Western Australia and Centre for Asthma Allergy and Respiratory Research, School of Medicine and Pharmacology, The University of Western Australia, Perth, WA, Australia.
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Laurent
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000502:physiology*; D008954:Models, Biological; D012038:Regeneration / Q000502:physiology*; D044968:Regenerative Medicine / Q000379:methods* / Q000639:trends; D013234:Stem Cells / Q000166:cytology*
keywords: Epithelium; Lung; Mesenchyme; Regeneration; Stem cells