Epithelial Repair and Regeneration

Brody, Steven L.; Atkinson, Jeffrey J.

doi:10.1007/978-0-387-72430-0_45

Cited by 3 publications

(4 citation statements)

References 102 publications

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“…Taken together, features of chronic lung diseases commonly include excessive inflammation, tissue remodelling, and epithelial damage, which ultimately leads to a loss of function and organ failure [2,3]. …”

Section: Introductionmentioning

confidence: 99%

Bone marrow-derived progenitor cells in end-stage lung disease patients

et al. 2013

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BackgroundChronic lung diseases are marked by progressive inflammation, tissue damage and remodelling. Bone marrow-derived progenitor cells may contribute to these processes. The objectives of this study were to (1) to quantify CD45+Collagen-1+ fibrocytes and a novel epithelial-like population of bone marrow-derived cells, which express Clara Cell Secretory Protein, in patients at the time of lung transplant and (2) to evaluate mediators that may act to recruit these cells during injury.MethodsUsing an observational design, progenitor cells were quantified by flow cytometry from both bone marrow (BM) and peripheral blood (PB). Migration was tested using in vitro transwell assays. Multiplex bead-based assays were used to quantify plasma cytokines.ResultsAn increase in CD45+Collagen-1+ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients. Cystic fibrosis patients had an increase in CCSP+ cells in both the BM and PB. The proportion of CCSP+ cells in the BM and PB was correlated. CCSP+ cells express the chemokine receptors CCR2, CCR4, CXCR3, and CXCR4, and significantly migrated in vitro toward Stromal Derived Factor-1 (SDF-1) and Stem Cell Growth Factor-β (SCGF-β). Plasma cytokine levels differed between disease groups, with a significant correlation between SCGF-β and CCSP+ cells and between Monocyte Chemotactic Protein-1 and fibrocytes.ConclusionsDifferent bone marrow-derived cells are found in various lung diseases. Increased fibrocytes were associated with fibrotic lung diseases. An increase in the novel CCSP+ epithelial-like progenitors in cystic fibrosis patients was found. These differences may be mediated by alterations in plasma cytokines responsible for cell recruitment.

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Section: Introductionmentioning

confidence: 99%

Bone marrow-derived progenitor cells in end-stage lung disease patients

et al. 2013

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“…The crosstalk between the stem cell and its niche profoundly affects stem cell behaviour and functionality. 3,[34][35][36][37] In the lung, the interdependence of regenerative cells and their niche microenvironment are evident both in the process of lung epithelial regeneration and repair, 38 and in the aberrant proliferation and differentiation of airway and alveolar epithelial cells as a consequence of the pathophysiological remodelling and scarring of the subepithelial microenvironment in lung fibrosis and asthma. [39][40][41][42]…”

Section: Stem Cells Are Defined In Context-the Role Of the Niche In Smentioning

confidence: 99%

Lung stem cells: Do they exist?

Bertoncello

McQualter

2013

Respirology

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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.Key words: adult stem cell, airway epithelium, animal model, cell biology, lung regeneration. 'Omnis cellula e cellula' Rudolf Virchow (1858)The identity of stem cells, their location and organization within tissues, and the regulation of their regenerative potential has been the subject of ongoing debate since articulation of modern cell theory in the mid-19th century, which recognized that cells are the fundamental building blocks of all living

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“…Analysis of genetically engineered mice has revealed that terminally differentiated ciliated airway epithelial cells are especially long lived, having an average half-life of 17 mo (37). Consequently, it is generally accepted that the adult lung epithelium is mitotically quiescent in the absence of injury (11,17,43) and that the very low basal rate of lung epithelial cell proliferation in the steady state is sufficient to account for replacement of airway and alveolar epithelial cells damaged by normal wear and tear.By comparison, little is known about the cell kinetic status of adult lung mesenchymal stromal cells in the steady state. Early studies reviewed by Kauffman (23) and by Evans and Shami (17) showed that the labeling index of lung interstitial fibroblasts in situ increased sharply to levels up to 8 -10 times higher than that of juxtaposed epithelial cells during perinatal lung growth and alveolar septation and then rapidly declined.…”

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confidence: 99%

mentioning

confidence: 99%

Mesenchymal stromal cell turnover in the normal adult lung revisited

Seyed‐Razavi

Williams

Winkler

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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neg CD31 neg Sca-1 pos lung cells following long-term feeding of BrdU to mice in their drinking water reveals that lung mesenchymal stromal cells cycle continuously throughout life. Analysis of BrdU incorporation during long-term feeding and during chasing (delabeling) following replacement of BrdU-water with normal water shows that the CD45 neg CD31 neg Sca-1 pos lung mesenchymal stromal cell compartment turns over at a rate of ϳ2.26% per day with a time to half-cycled of 44 days, an estimated cell proliferation rate of 0.004/ day, and a cell death rate of 0.018/day. lung mesenchymal stromal cells; bromodeoxyuridine; cell cycling; cell turnover IN A BRIEF REVIEW PUBLISHED in 1983, documenting information about cell kinetics and cell turnover in the lung, Bowden (7) pertinently stated that "the study of cellular kinetics in the normal lung is prerequisite to an understanding of the pulmonary responses to injury and of the processes that initiate and control cellular regeneration and repair." It is therefore surprising that, despite the burgeoning interest in lung regeneration and repair in recent years, the field largely continues to rely on estimates of lung cell cycling and turnover in the steady state that predate that review (23,44).Those studies employed classical autoradiographic techniques and histomorphometry (17,47) to analyze the cell kinetics of often ill-defined cell populations in tracheal, bronchiolar, and alveolar regions of the lung, mostly in neonatal and young animals. They concluded that adult mouse lung bronchiolar and alveolar epithelial cell lineages turned over at a rate of no more than 1% per day in the steady state (7,13,23,44,45). More recent studies measuring bromodeoxyuridine (BrdU) incorporation in airway and alveolar epithelial cells by flow cytometry (42,46) or immunohistological analysis (38) are in broad agreement with this estimate. Analysis of genetically engineered mice has revealed that terminally differentiated ciliated airway epithelial cells are especially long lived, having an average half-life of 17 mo (37). Consequently, it is generally accepted that the adult lung epithelium is mitotically quiescent in the absence of injury (11,17,43) and that the very low basal rate of lung epithelial cell proliferation in the steady state is sufficient to account for replacement of airway and alveolar epithelial cells damaged by normal wear and tear.By comparison, little is known about the cell kinetic status of adult lung mesenchymal stromal cells in the steady state. Early studies reviewed by Kauffman (23) and by Evans and Shami (17) showed that the labeling index of lung interstitial fibroblasts in situ increased sharply to levels up to 8 -10 times higher than that of juxtaposed epithelial cells during perinatal lung growth and alveolar septation and then rapidly declined. Recent analysis of lung regeneration in adult mice postpneumonectomy also reveals a rapid but transient increase in the proliferative activity of lung mesenchymal stromal cells in the days immediately followin...

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Epithelial Repair and Regeneration

Cited by 3 publications

References 102 publications

Bone marrow-derived progenitor cells in end-stage lung disease patients

Bone marrow-derived progenitor cells in end-stage lung disease patients

Lung stem cells: Do they exist?

Mesenchymal stromal cell turnover in the normal adult lung revisited

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