Neuroepithelial Bodies of Pulmonary Airways Serve as a Reservoir of Progenitor Cells Capable of Epithelial Regeneration

Reynolds, Susan D.; Giangreco, Adam; Power, John H.; Stripp, Barry R.

doi:10.1016/s0002-9440(10)64727-x

Cited by 401 publications

(357 citation statements)

References 46 publications

(42 reference statements)

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“…Clara-like cells are another cell type that exhibits many features of pluripotent stem cells and apparently contributes to epithelial regeneration [120][121][122]. They can be discriminated from Clara cells by their resistance to naphthalene and their close association with pulmonary neuroepithelial bodies (NEBs) [123,124]. ATP released from secretory vesicles of rodent NEBs [125] in response to depolarization in lung slices promotes paracrine effects on surrounding Clara-like cells by activation of P2Y2 receptors.…”

Section: Pulmonary Epithelium Injurymentioning

confidence: 99%

“…ATP released from secretory vesicles of rodent NEBs [125] in response to depolarization in lung slices promotes paracrine effects on surrounding Clara-like cells by activation of P2Y2 receptors. Considering the stem cell-like characteristics of Clara-like cells, this purinergic signaling might be of great importance for airway epithelial repair after injury [123].…”

Section: Pulmonary Epithelium Injurymentioning

confidence: 99%

“…ATP-mediated P2 purinergic receptor activation promotes bronchial epithelial migration and epithelial repair. This is suggested to occur after activation of dual oxidase 1 mediated by release of ATP during injury [123]. In addition, adenosine also stimulates cell migration, proliferation, and angiogenesis [129,130].…”

Section: Pulmonary Epithelium Injurymentioning

confidence: 99%

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Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Glaser

Cappellari

Pillat

et al. 2011

Purinergic Signalling

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Replacement of lost or dysfunctional tissues by stem cells has recently raised many investigations on therapeutic applications. Purinergic signaling has been shown to regulate proliferation, differentiation, cell death, and successful engraftment of stem cells originated from diverse origins. Adenosine triphosphate release occurs in a controlled way by exocytosis, transporters, and lysosomes or in large amounts from damaged cells, which is then subsequently degraded into adenosine. Paracrine and autocrine mechanisms induced by immune responses present critical factors for the success of stem cell therapy. While P1 receptors generally exert beneficial effects including anti-inflammatory activity, P2 receptor-mediated actions depend on the subtype of stimulated receptors and localization of tissue repair. Pro-inflammatory actions and excitatory tissue damages mainly result from P2X7 receptor activation, while other purinergic receptor subtypes participate in proliferation and differentiation, thereby providing adequate niches for stem cell engraftment and novel mechanisms for cell therapy and endogenous tissue repair. Therapeutic applications based on regulation of purinergic signaling are foreseen for kidney and heart muscle regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial cells as well as for induction of neurogenesis in case of neurodegenerative diseases.

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Section: Pulmonary Epithelium Injurymentioning

confidence: 99%

Section: Pulmonary Epithelium Injurymentioning

confidence: 99%

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Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Glaser

Cappellari

Pillat

et al. 2011

Purinergic Signalling

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“…In the bronchiolar epithelium, stem cell function appears to be the property of rare pollutant-resistant CE cells, co-localized with pulmonary neuroendocrine cells (PNECs), normally located in cell clusters termed neuroepithelial bodies (NEBs); PNECs can only act as progenitors for more PNECs [158]. Pollutant resistance of CE cells is related to a deficiency in the phase I drug-metabolizing enzyme CYP450 2F2.…”

Section: Lungmentioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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“…11,12 Progenitor cells of the bronchiolar conducting airway include Clara cell secretory protein (CCSP)-expressing (CE) cells in addition to a rare population of calcitonin gene-related peptide (CGRP)-expressing cells. 11,14 Of these bronchiolar airway progenitor pools, CE cells represent a multipotent progenitor population. 11 CCSP-expressing cells can be further subdivided according to their susceptibility to naphthalene; naphthalene-sensitive CE cells are more numerous and represent the classical nonciliated secretory (Clara) cell, whereas naphthalene-resistant CE cells represent a rare subpopulation of CE cells that localize to distinct airway microenvironments and have properties of tissue-specific stem cells.…”

mentioning

confidence: 99%

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

Hong

Reynolds

Watkins

et al. 2004

The American Journal of Pathology

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475

390

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Commitment of the pulmonary epithelium to bronchial and bronchiolar airway lineages occurs during the transition from pseudoglandular to cannalicular phases of lung development, suggesting that regional differences exist with respect to the identity of stem and progenitor cells that contribute to epithelial maintenance in adulthood. We previously defined a critical role for Clara cell secretory protein-expressing (CE) cells in renewal of bronchiolar airway epithelium following injury. Even though CE cells are also the principal progenitor for maintenance of the bronchial airway epithelium, CE cell injury is resolved through a mechanism involving recruitment of a second progenitor cell population that we now identify as a GSI-B 4 reactive, cytokeratin-14-expressing basal cell. These cells exhibit multipotent differentiation capacity as assessed by analysis of cellular phenotype within clones of LacZ-tagged cells. Clones were derived from K14-expressing cells tagged in a cell-type-specific fashion by ligand-regulable Cre recombinase-mediated genomic rearrangement of the ROSA26 recombination substrate allele. We conclude that basal cells represent an alternative multipotent progenitor cell population of bronchial airways and that progenitor cell selection is dictated by the type of airway injury. Conducting airways of the lung are lined by a highly specialized epithelium whose composition and function varies along the proximal to distal axis. Despite a growing appreciation of mechanisms contributing to branching morphogenesis and lineage specification in the developing lung it is still unclear how a complex epithelium such as that present in the conducting airway is established and maintained through adulthood. Studies in the developing rat lung indicate that lineage restriction occurs during the transition from the pseudoglandular to cannalicular phases of lung development. At this time cells of the proximal airway lose the ability to respond to mesenchymally derived signals capable of inducing distal airway differentiation.

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Neuroepithelial Bodies of Pulmonary Airways Serve as a Reservoir of Progenitor Cells Capable of Epithelial Regeneration

Cited by 401 publications

References 46 publications

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Attributes of adult stem cells

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

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