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National Heart, Lung, and Blood Institute perspective: lung progenitor and stem cells--gaps in knowledge and future opportunities.

Blaisdell CJ, Gail DB, Nabel EG - Stem Cells (2009)

Bottom Line: Because the lung stem cell field is so new, there remain many unanswered questions that are being addressed regarding the identification, location, and role of exogenous and endogenous stem and progenitor cell populations in growth, regeneration, and repair of the lung.Advancing lung stem cell biology will require multidisciplinary teams and a long term effort to unravel the biologic processes of stem cells in the lung.While no clinical research in lung stem cell therapies are currently funded by NHLBI, the knowledge gained by understanding the basic biology of the lung stem cell populations will be needed to translate to diagnostic and therapeutic strategies in the future.

View Article: PubMed Central - PubMed

Affiliation: National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. blaisdellcj@nhlbi.nih.gov

ABSTRACT
Because the lung stem cell field is so new, there remain many unanswered questions that are being addressed regarding the identification, location, and role of exogenous and endogenous stem and progenitor cell populations in growth, regeneration, and repair of the lung. Advancing lung stem cell biology will require multidisciplinary teams and a long term effort to unravel the biologic processes of stem cells in the lung. While no clinical research in lung stem cell therapies are currently funded by NHLBI, the knowledge gained by understanding the basic biology of the lung stem cell populations will be needed to translate to diagnostic and therapeutic strategies in the future.

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Illustration of putative stem cell niches in the adult mouse lung. Epithelia of the adult mouse lung can be divided into four major, biologically distinct trophic units (trachea, bronchi, bronchioles, and alveoli), each of which encompasses unique types of airway epithelial cells (epithelia relevant to each unit are shown inside circles). Five potential stem cell niches for these various trophic units are shown on the right, with locations of candidate stem cells marked by arrowheads (cells are in red). Stem cells and niches include the following: 1, an unknown cell type in the SMG ducts of the proximal trachea; 2, basal cells in the intercartilaginous zones of the lower trachea and bronchi (these structures may also be associated with innervated NEBs; 3, variant Clara cells associated with NEBs in bronchioles; 4, Clara cell associated with BADJ; and 5, alveolar type II cells of the alveoli. Abbreviations: BADJ, bronchiolar alveolar duct junctions; Clarav, variant Clara cells; NEB, neuroendocrine body; SMG, submucosal gland. (From Liu X, Engelhardt JF. The glandular stem/progenitor cell niche in airway development and repair. Proc Am Thorac Soc 2008;5:682-688.)
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fig02: Illustration of putative stem cell niches in the adult mouse lung. Epithelia of the adult mouse lung can be divided into four major, biologically distinct trophic units (trachea, bronchi, bronchioles, and alveoli), each of which encompasses unique types of airway epithelial cells (epithelia relevant to each unit are shown inside circles). Five potential stem cell niches for these various trophic units are shown on the right, with locations of candidate stem cells marked by arrowheads (cells are in red). Stem cells and niches include the following: 1, an unknown cell type in the SMG ducts of the proximal trachea; 2, basal cells in the intercartilaginous zones of the lower trachea and bronchi (these structures may also be associated with innervated NEBs; 3, variant Clara cells associated with NEBs in bronchioles; 4, Clara cell associated with BADJ; and 5, alveolar type II cells of the alveoli. Abbreviations: BADJ, bronchiolar alveolar duct junctions; Clarav, variant Clara cells; NEB, neuroendocrine body; SMG, submucosal gland. (From Liu X, Engelhardt JF. The glandular stem/progenitor cell niche in airway development and repair. Proc Am Thorac Soc 2008;5:682-688.)

Mentions: Unlike the hematopoietic stem cell hierarchy, little is known about specific cells in the lung that have the capacity to self-renew, the organization of stem/progenitor cells in the lung and whether it conforms to a classic or a nonclassic stem cell hierarchy, and the differentiation pathways for the more than 40 phenotypically and functionally distinct types of cells that are required for air to be conducted to alveoli and transfer of oxygen and carbon dioxide into and out of the blood. There are at least five putative epithelial stem/progenitor cell niches in the adult mouse airway [7] (Fig. 2), as well as endothelial stem cells in the pulmonary vasculature and airway smooth muscle stem cells. In addition, many cells have host defense properties that are needed to protect the lung against inhaled particles of pollutants, microorganisms, and antigens. The human lung has 26 branches of airways that lead to alveoli with a surface area for gas exchange of 100 m2. Repair after injury to different regions of the lung is expected to require different populations of stem cells for regeneration. As airways develop, there is close proximity of the developing pulmonary vascular system and cross-talk between endothelial precursors and the epithelium for normal lung development to occur [8,9]. As with the pulmonary epithelium, different cellular subpopulations of the pulmonary endothelium probably have distinct embryonic origins.


National Heart, Lung, and Blood Institute perspective: lung progenitor and stem cells--gaps in knowledge and future opportunities.

Blaisdell CJ, Gail DB, Nabel EG - Stem Cells (2009)

Illustration of putative stem cell niches in the adult mouse lung. Epithelia of the adult mouse lung can be divided into four major, biologically distinct trophic units (trachea, bronchi, bronchioles, and alveoli), each of which encompasses unique types of airway epithelial cells (epithelia relevant to each unit are shown inside circles). Five potential stem cell niches for these various trophic units are shown on the right, with locations of candidate stem cells marked by arrowheads (cells are in red). Stem cells and niches include the following: 1, an unknown cell type in the SMG ducts of the proximal trachea; 2, basal cells in the intercartilaginous zones of the lower trachea and bronchi (these structures may also be associated with innervated NEBs; 3, variant Clara cells associated with NEBs in bronchioles; 4, Clara cell associated with BADJ; and 5, alveolar type II cells of the alveoli. Abbreviations: BADJ, bronchiolar alveolar duct junctions; Clarav, variant Clara cells; NEB, neuroendocrine body; SMG, submucosal gland. (From Liu X, Engelhardt JF. The glandular stem/progenitor cell niche in airway development and repair. Proc Am Thorac Soc 2008;5:682-688.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2962803&req=5

fig02: Illustration of putative stem cell niches in the adult mouse lung. Epithelia of the adult mouse lung can be divided into four major, biologically distinct trophic units (trachea, bronchi, bronchioles, and alveoli), each of which encompasses unique types of airway epithelial cells (epithelia relevant to each unit are shown inside circles). Five potential stem cell niches for these various trophic units are shown on the right, with locations of candidate stem cells marked by arrowheads (cells are in red). Stem cells and niches include the following: 1, an unknown cell type in the SMG ducts of the proximal trachea; 2, basal cells in the intercartilaginous zones of the lower trachea and bronchi (these structures may also be associated with innervated NEBs; 3, variant Clara cells associated with NEBs in bronchioles; 4, Clara cell associated with BADJ; and 5, alveolar type II cells of the alveoli. Abbreviations: BADJ, bronchiolar alveolar duct junctions; Clarav, variant Clara cells; NEB, neuroendocrine body; SMG, submucosal gland. (From Liu X, Engelhardt JF. The glandular stem/progenitor cell niche in airway development and repair. Proc Am Thorac Soc 2008;5:682-688.)
Mentions: Unlike the hematopoietic stem cell hierarchy, little is known about specific cells in the lung that have the capacity to self-renew, the organization of stem/progenitor cells in the lung and whether it conforms to a classic or a nonclassic stem cell hierarchy, and the differentiation pathways for the more than 40 phenotypically and functionally distinct types of cells that are required for air to be conducted to alveoli and transfer of oxygen and carbon dioxide into and out of the blood. There are at least five putative epithelial stem/progenitor cell niches in the adult mouse airway [7] (Fig. 2), as well as endothelial stem cells in the pulmonary vasculature and airway smooth muscle stem cells. In addition, many cells have host defense properties that are needed to protect the lung against inhaled particles of pollutants, microorganisms, and antigens. The human lung has 26 branches of airways that lead to alveoli with a surface area for gas exchange of 100 m2. Repair after injury to different regions of the lung is expected to require different populations of stem cells for regeneration. As airways develop, there is close proximity of the developing pulmonary vascular system and cross-talk between endothelial precursors and the epithelium for normal lung development to occur [8,9]. As with the pulmonary epithelium, different cellular subpopulations of the pulmonary endothelium probably have distinct embryonic origins.

Bottom Line: Because the lung stem cell field is so new, there remain many unanswered questions that are being addressed regarding the identification, location, and role of exogenous and endogenous stem and progenitor cell populations in growth, regeneration, and repair of the lung.Advancing lung stem cell biology will require multidisciplinary teams and a long term effort to unravel the biologic processes of stem cells in the lung.While no clinical research in lung stem cell therapies are currently funded by NHLBI, the knowledge gained by understanding the basic biology of the lung stem cell populations will be needed to translate to diagnostic and therapeutic strategies in the future.

View Article: PubMed Central - PubMed

Affiliation: National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. blaisdellcj@nhlbi.nih.gov

ABSTRACT
Because the lung stem cell field is so new, there remain many unanswered questions that are being addressed regarding the identification, location, and role of exogenous and endogenous stem and progenitor cell populations in growth, regeneration, and repair of the lung. Advancing lung stem cell biology will require multidisciplinary teams and a long term effort to unravel the biologic processes of stem cells in the lung. While no clinical research in lung stem cell therapies are currently funded by NHLBI, the knowledge gained by understanding the basic biology of the lung stem cell populations will be needed to translate to diagnostic and therapeutic strategies in the future.

Show MeSH
Related in: MedlinePlus