The Experts below are selected from a list of 207 Experts worldwide ranked by ideXlab platform
Carla F. Kim - One of the best experts on this subject based on the ideXlab platform.
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Lung Stem and progenitor Cells in tissue homeostasis and disease.
Current topics in developmental biology, 2014Co-Authors: Kristen T. Leeman, Christine M. Fillmore, Carla F. KimAbstract:The mammalian Lung is a complex organ containing numerous putative Stem/progenitor Cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these Cell populations in the context of Lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several Lung Stem and progenitor Cell populations in vivo during different types of Lung injury repair. Using specific sets of Cell surface markers, these Cells can also be isolated from murine and human Lung and tested in 3D culture syStems and in vivo transplant assays. The pathology of devastating Lung diseases, including Lung cancers, is likely in part due to dysregulation and dysfunction of Lung Stem Cells. More precise characterization of Stem Cells with identification of new, unique markers; improvement in isolation and transplant techniques; and further development of functional assays will ultimately lead to new therapies for a host of human Lung diseases. In particular, Lung cancer biology may be greatly informed by findings in normal Lung Stem Cell biology as evidence suggests that Lung cancer is a disease that begins in, and may be driven by, neoplastic Lung Stem Cells.
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Stem Cell biology in the Lung and Lung cancers: using pulmonary context and classic approaches.
Cold Spring Harbor symposia on quantitative biology, 2008Co-Authors: David M. Raiser, Sima Zacharek, Rebecca R. Roach, Stephen J. Curtis, Kerstin W. Sinkevicius, David W. Gludish, Carla F. KimAbstract:Classic Stem Cell biology approaches tailored specifically with Lung biology in mind are needed to bring the field of Lung Stem Cell biology up to speed with that in other tissues. The infrequent Cellular turnover, the diversity of Cell types, and the neces sity of daily Cell function in this organ must be considered in Stem Cell studies. Previous work has created a base from which to explore transplantation, label retention, and more sophisticated lineage-tracing schemes to identify and characterize Stem Cell populations in the normal Lung. These approaches are also imperative for building on precedents set in other tissues in the exploration of the cancer Stem Cell hypothesis in Lung cancers. Additionally, recent studies provide key leads to further explore the molecular mechanisms that regulate Lung homeostasis. Here, we discuss strategies to advance the field of Lung Stem Cell biology with an emphasis on developing new, Lung-specific tools.
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Paving the road for Lung Stem Cell biology: bronchioalveolar Stem Cells and other putative distal Lung Stem Cells
American journal of physiology. Lung cellular and molecular physiology, 2007Co-Authors: Carla F. KimAbstract:New discoveries in Stem Cell biology are making the biology of solid tissues increasingly complex. Important seminal studies demonstrating the presence of damage-resistant Cell populations together with new isolation and characterization techniques suggest that Stem Cells exist in the adult Lung. More detailed in vivo molecular and Cellular characterization of bronchioalveolar Stem Cells (BASCs), other putative Lung Stem and progenitor Cells, and differentiated Cells is needed to determine the lineage relationships in adult Lung. Lung diseases such as cystic fibrosis or chronic obstructive pulmonary disease, as well as the most common form of Lung cancer in the United States, all involve apparent bronchiolar and alveolar Cell defects. It is likely that the delicate balance of Stem, progenitor, and differentiated Cell functions in the Lung is critically affected in patients with these devastating diseases. Thus the discovery of BASCs and other putative Lung Stem Cells will lay the foundation for new inroads to understanding Lung biology related to Lung disease.
Tomoko Betsuyaku - One of the best experts on this subject based on the ideXlab platform.
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Calorie restriction enhances adult mouse Lung Stem Cells function and reverses several ageing-induced changes.
Journal of tissue engineering and regenerative medicine, 2019Co-Authors: Ahmed E. Hegab, Makoto Ishii, Mari Ozaki, Fatma Y. Meligy, Makoto Nishino, Shizuko Kagawa, Tomoko BetsuyakuAbstract:Ageing is associated with decreased Lung function and an increased incidence of Lung infections. Several studies have suggested that long-term calorie restriction (CR) promotes health and longevity and results in the reduced risk of several diseases. The effect of CR is thought to be through improving the function of tissue Stem Cells. Stem Cell function is known to decline with ageing. In this study, we examined the effects of ageing on Lung epithelial and Stem Cells and the effect of CR on young and old Lungs. We found that ageing results in a decrease in tracheal basal Stem Cells. CR induced an increase in basal Stem Cells in both young and old mice. In addition, ageing induced Lung inflammation, and CR tended to reduce baseline Lung inflammatory Cell infiltration in young mice and significantly reduced ageing-induced Lung inflammation. Furthermore, ageing reduced the number and function of mitochondria in Lung and increased the level of mitochondrial reactive oxygen species. CR increased the number and function of mitochondria both in young and old mice. Moreover, ageing reduced Lung Stem Cell colony-forming efficiency (CFE), and CR increased the CFE in both young and old mice. Finally, CR improved epithelial Cell survival in injured Lungs of young mice. In conclusion, ageing causes several structural and functional changes/impairments in Lung epithelial Cells. CR induces several potentially beneficial changes in Lung epithelial Cells, even when it is initiated at an older age, including reversal of some ageing-induced changes.
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Mimicking the niche of Lung epithelial Stem Cells and characterization of several effectors of their in vitro behavior.
Stem cell research, 2015Co-Authors: Ahmed E. Hegab, Daisuke Arai, Jingtao Gao, Aoi Kuroda, Hiroyuki Yasuda, Makoto Ishii, Katsuhiko Naoki, Kenzo Soejima, Tomoko BetsuyakuAbstract:The niche surrounding Stem Cells regulate their fate during homeostasis and after injury or infection. The 3D organoid assay has been widely used to study Stem Cells behavior based on its capacity to evaluate self-renewal, differentiation and the effect of various medium supplements, drugs and co-culture with supportive Cells. We established an assay to study both Lung and trachea Stem Cells in vitro. We characterized their proliferation and differentiation spectrum at baseline then evaluated the effect of co-culturing with fibroblasts and endothelial Cells and/or treating with several biologically relevant substances as possible contributors to their niche. We found that Lung epithelial (but not tracheal basal) Stem Cells require co-culture with stromal Cells to undergo clonal proliferation and differentiation. Fibroblasts were more efficient than endothelial Cells in offering this support and the pattern of support varied based on the tissue origin of the stromal Cells. Treating distal Lung epithelial or basal Stem Cells with FGF2, FGF9, FGF10, LIF as well as ALK5 and ROCK inhibitors increased their colony formation efficiency and resulted in variable effects on colonies number, size and differentiation spectrum. This model and findings pave the way for better understanding of Lung Stem Cell niche components and factors that can manipulate Lung Stem Cell behavior.
Barry R. Stripp - One of the best experts on this subject based on the ideXlab platform.
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hyaluronan and tlr4 promote surfactant protein c positive alveolar progenitor Cell renewal and prevent severe pulmonary fibrosis in mice
Nature Medicine, 2016Co-Authors: Jiurong Liang, Yanli Zhang, Ting Xie, Ningshan Liu, Huaiyong Chen, Yan Geng, Adrianne Kurkciyan, Jessica Monterrosa Mena, Barry R. StrippAbstract:Successful recovery from Lung injury requires the repair and regeneration of alveolar epithelial Cells to restore the integrity of gas-exchanging regions within the Lung and preserve organ function. Improper regeneration of the alveolar epithelium is often associated with severe pulmonary fibrosis, the latter of which involves the recruitment and activation of fibroblasts, as well as matrix accumulation. Type 2 alveolar epithelial Cells (AEC2s) are Stem Cells in the adult Lung that contribute to the Lung repair process. The mechanisms that regulate AEC2 renewal are incompletely understood. We provide evidence that expression of the innate immune receptor Toll-like receptor 4 (TLR4) and the extraCellular matrix glycosaminoglycan hyaluronan (HA) on AEC2s are important for AEC2 renewal, repair of Lung injury and limiting the extent of fibrosis. Either deletion of TLR4 or HA synthase 2 in surfactant-protein-C-positive AEC2s leads to impaired renewal capacity, severe fibrosis and mortality. Furthermore, AEC2s from patients with severe pulmonary fibrosis have reduced Cell surface HA and impaired renewal capacity, suggesting that HA and TLR4 are key contributors to Lung Stem Cell renewal and that severe pulmonary fibrosis is the result of distal epithelial Stem Cell failure.
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Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor Cell renewal and prevent severe pulmonary fibrosis in mice
Nature Medicine, 2016Co-Authors: Jiurong Liang, Barry R. Stripp, Yanli Zhang, Ting Xie, Ningshan Liu, Huaiyong Chen, Yan Geng, Adrianne Kurkciyan, Jessica Monterrosa Mena, Dianhua JiangAbstract:Successful recovery from Lung injury requires the repair and regeneration of alveolar epithelial Cells to restore the integrity of gas-exchanging regions within the Lung and preserve organ function. Improper regeneration of the alveolar epithelium is often associated with severe pulmonary fibrosis, the latter of which involves the recruitment and activation of fibroblasts, as well as matrix accumulation. Type 2 alveolar epithelial Cells (AEC2s) are Stem Cells in the adult Lung that contribute to the Lung repair process. The mechanisms that regulate AEC2 renewal are incompletely understood. We provide evidence that expression of the innate immune receptor Toll-like receptor 4 (TLR4) and the extraCellular matrix glycosaminoglycan hyaluronan (HA) on AEC2s are important for AEC2 renewal, repair of Lung injury and limiting the extent of fibrosis. Either deletion of TLR4 or HA synthase 2 in surfactant-protein-C-positive AEC2s leads to impaired renewal capacity, severe fibrosis and mortality. Furthermore, AEC2s from patients with severe pulmonary fibrosis have reduced Cell surface HA and impaired renewal capacity, suggesting that HA and TLR4 are key contributors to Lung Stem Cell renewal and that severe pulmonary fibrosis is the result of distal epithelial Stem Cell failure. Reduced hyaluronan–TLR4 signaling in a Stem Cell population of the Lung contributes to a lack of renewal of these Cells and promotes fibrosis in patients with idiopathic pulmonary fibrosis.
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Does a Lung Stem Cell Exist
Lung Stem Cells in the Epithelium and Vasculature, 2015Co-Authors: Samriddha Ray, Barry R. StrippAbstract:Cells of Lung epithelium are under a slow constant turn over in steady state and subject to rapid regeneration upon injury by inhaled or syStemic pneumotoxicants. Multiple pools of adult Stem Cells have been shown to be involved in steady state airway maintenance and regeneration following injury. In this chapter, we summarize Cellular diversity within adult mammalian airway epithelium that underscores challenges in maintenance and repair of the airway. We then briefly discuss distribution, mechanisms of identification and regulation of resident Stem, and progenitor Cell pools under steady state and in context of different injury models in mice. The ensuing chapters discuss some of these concepts at greater length and detail.
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Lung Stem Cell differentiation in mice directed by endothelial Cells via a bmp4 nfatc1 thrombospondin 1 axis
Cell, 2014Co-Authors: Dong Ha Bhang, Barry R. Stripp, Alexander M Beede, Tian Lian Huang, Kenneth D Bloch, Amy J Wagers, Yuhua TsengAbstract:Summary Lung Stem Cells are instructed to produce lineage-specific progeny through unknown factors in their microenvironment. We used clonal 3D cocultures of endothelial Cells and distal Lung Stem Cells, bronchioalveolar Stem Cells (BASCs), to probe the instructive mechanisms. Single BASCs had bronchiolar and alveolar differentiation potential in Lung endothelial Cell cocultures. Gain- and loss-of-function experiments showed that BMP4-Bmpr1a signaling triggers calcineurin/NFATc1-dependent expression of thrombospondin-1 ( Tsp1 ) in Lung endothelial Cells to drive alveolar lineage-specific BASC differentiation. Tsp1 null mice exhibited defective alveolar injury repair, confirming a crucial role for the BMP4-NFATc1-TSP1 axis in Lung epithelial differentiation and regeneration in vivo. Discovery of this pathway points to methods to direct the derivation of specific Lung epithelial lineages from multipotent Cells. These findings elucidate a pathway that may be a critical target in Lung diseases and provide tools to understand the mechanisms of respiratory diseases at the single-Cell level.
Ahmed E. Hegab - One of the best experts on this subject based on the ideXlab platform.
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Calorie restriction enhances adult mouse Lung Stem Cells function and reverses several ageing-induced changes.
Journal of tissue engineering and regenerative medicine, 2019Co-Authors: Ahmed E. Hegab, Makoto Ishii, Mari Ozaki, Fatma Y. Meligy, Makoto Nishino, Shizuko Kagawa, Tomoko BetsuyakuAbstract:Ageing is associated with decreased Lung function and an increased incidence of Lung infections. Several studies have suggested that long-term calorie restriction (CR) promotes health and longevity and results in the reduced risk of several diseases. The effect of CR is thought to be through improving the function of tissue Stem Cells. Stem Cell function is known to decline with ageing. In this study, we examined the effects of ageing on Lung epithelial and Stem Cells and the effect of CR on young and old Lungs. We found that ageing results in a decrease in tracheal basal Stem Cells. CR induced an increase in basal Stem Cells in both young and old mice. In addition, ageing induced Lung inflammation, and CR tended to reduce baseline Lung inflammatory Cell infiltration in young mice and significantly reduced ageing-induced Lung inflammation. Furthermore, ageing reduced the number and function of mitochondria in Lung and increased the level of mitochondrial reactive oxygen species. CR increased the number and function of mitochondria both in young and old mice. Moreover, ageing reduced Lung Stem Cell colony-forming efficiency (CFE), and CR increased the CFE in both young and old mice. Finally, CR improved epithelial Cell survival in injured Lungs of young mice. In conclusion, ageing causes several structural and functional changes/impairments in Lung epithelial Cells. CR induces several potentially beneficial changes in Lung epithelial Cells, even when it is initiated at an older age, including reversal of some ageing-induced changes.
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Mimicking the niche of Lung epithelial Stem Cells and characterization of several effectors of their in vitro behavior.
Stem cell research, 2015Co-Authors: Ahmed E. Hegab, Daisuke Arai, Jingtao Gao, Aoi Kuroda, Hiroyuki Yasuda, Makoto Ishii, Katsuhiko Naoki, Kenzo Soejima, Tomoko BetsuyakuAbstract:The niche surrounding Stem Cells regulate their fate during homeostasis and after injury or infection. The 3D organoid assay has been widely used to study Stem Cells behavior based on its capacity to evaluate self-renewal, differentiation and the effect of various medium supplements, drugs and co-culture with supportive Cells. We established an assay to study both Lung and trachea Stem Cells in vitro. We characterized their proliferation and differentiation spectrum at baseline then evaluated the effect of co-culturing with fibroblasts and endothelial Cells and/or treating with several biologically relevant substances as possible contributors to their niche. We found that Lung epithelial (but not tracheal basal) Stem Cells require co-culture with stromal Cells to undergo clonal proliferation and differentiation. Fibroblasts were more efficient than endothelial Cells in offering this support and the pattern of support varied based on the tissue origin of the stromal Cells. Treating distal Lung epithelial or basal Stem Cells with FGF2, FGF9, FGF10, LIF as well as ALK5 and ROCK inhibitors increased their colony formation efficiency and resulted in variable effects on colonies number, size and differentiation spectrum. This model and findings pave the way for better understanding of Lung Stem Cell niche components and factors that can manipulate Lung Stem Cell behavior.
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dynamic changes in intraCellular ros levels regulate airway basal Stem Cell homeostasis through nrf2 dependent notch signaling
Cell Stem Cell, 2014Co-Authors: Manash K Paul, Ahmed E. Hegab, Bharti Bisht, Daphne O Darmawan, Richard Chiou, William D Wallace, Andrew T Chon, Tristan Grogan, David Elashoff, Jackelyn A AlvaornelasAbstract:Airways are exposed to myriad environmental and damaging agents such as reactive oxygen species (ROS), which also have physiological roles as signaling molecules that regulate Stem Cell function. However, the functional significance of both steady and dynamically changing ROS levels in different Stem Cell populations, as well as downstream mechanisms that integrate ROS sensing into decisions regarding Stem Cell homeostasis, are unclear. Here, we show in mouse and human airway basal Stem Cells (ABSCs) that intraCellular flux from low to moderate ROS levels is required for Stem Cell self-renewal and proliferation. Changing ROS levels activate Nrf2, which activates the Notch pathway to stimulate ABSC self-renewal and an antioxidant program that scavenges intraCellular ROS, returning overall ROS levels to a low state to maintain homeostatic balance. This redox-mediated regulation of Lung Stem Cell function has significant implications for Stem Cell biology, repair of Lung injuries, and diseases such as cancer.
R Ilona Linnoila - One of the best experts on this subject based on the ideXlab platform.
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Functional facets of the pulmonary neuroendocrine syStem
Laboratory Investigation, 2006Co-Authors: R Ilona LinnoilaAbstract:Pulmonary neuroendocrine Cells (PNECs) have been around for 60 years in the scientific literature, although phylogenetically they are ancient. Their traditionally ascribed functions include chemoreception and regulation of Lung maturation and growth. There is recent evidence that neuroendocrine (NE) differentiation in the Lung is regulated by genes and pathways that are conserved in the development of the nervous syStem from Drosophila to humans (such as achaete-scute homolog-1 ), or implicated in the carcinogenesis of the nervous or NE syStem (such as the retinoblastoma tumor suppressor gene). In addition, complex neural networks are in place to regulate chemosensory and other functions. Even solitary PNECs appear to be innervated. For the first time ever, we have mouse models for Lung NE carcinomas, including the most common and virulent small Cell Lung carcinoma. Moreover, PNECs may be important for inflammatory responses, and pivotal for Lung Stem Cell niches. These discoveries signify an exciting new era for PNECs and are likely to have therapeutic and diagnostic applications.
