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https://www.readbyqxmd.com/read/28922348/stem-cell-biology-and-regenerative-medicine-for-neonatal-lung-diseases
#1
REVIEW
Martin Kang, Bernard Thébaud
Lung diseases remain one of the main causes of morbidity and mortality in neonates. Cell therapy and regenerative medicine have the potential to revolutionize the management of life-threatening and debilitating lung diseases that currently lack effective treatments. Over the past decade, the repair capabilities of stem/progenitor cells has been harnessed to prevent/rescue lung damage in experimental neonatal lung diseases. Mesenchymal stromal cells and amnion epithelial cells exert pleiotropic effects and represent ideal therapeutic cells for bronchopulmonary dysplasia, a multifactorial disease...
September 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28916766/stimulatory-secretions-of-airway-epithelial-cells-accelerate-early-repair-of-tracheal-epithelium
#2
Egi Kardia, Rafeezul Mohamed, Badrul Hisham Yahaya
Airway stem/progenitor epithelial cells (AECs) are notable for their differentiation capacities in response to lung injury. Our previous finding highlighted the regenerative capacity of AECs following transplantation in repairing tracheal injury and reducing the severity of alveolar damage associated acute lung injury in a rabbit model. The goal of this study is to further investigate the potential of AECs to re-populate the tracheal epithelium and to study their stimulatory effect on inhibiting pro-inflammatory cytokines, epithelial cell migration and proliferation, and epithelial-to-mesenchymal transition (EMT) process following tracheal injury...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915889/anti-fibrotic-efficacy-of-nintedanib-in-pulmonary-fibrosis-via-the-inhibition-of-fibrocyte-activity
#3
Seidai Sato, Shintaro Shinohara, Shinya Hayashi, Shun Morizumi, Shuichi Abe, Hiroyasu Okazaki, Yanjuan Chen, Hisatsugu Goto, Yoshinori Aono, Hirohisa Ogawa, Kazuya Koyama, Haruka Nishimura, Hiroshi Kawano, Yuko Toyoda, Hisanori Uehara, Yasuhiko Nishioka
BACKGROUND: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear...
September 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28886383/anatomically-and-functionally-distinct-lung-mesenchymal-populations-marked-by-lgr5-and-lgr6
#4
Joo-Hyeon Lee, Tuomas Tammela, Matan Hofree, Jinwook Choi, Nemanja Despot Marjanovic, Seungmin Han, David Canner, Katherine Wu, Margherita Paschini, Dong Ha Bhang, Tyler Jacks, Aviv Regev, Carla F Kim
The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6(+) cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation...
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28886382/distinct-mesenchymal-lineages-and-niches-promote-epithelial-self-renewal-and-myofibrogenesis-in-the-lung
#5
Jarod A Zepp, William J Zacharias, David B Frank, Christina A Cavanaugh, Su Zhou, Michael P Morley, Edward E Morrisey
The lung is an architecturally complex organ comprising a heterogeneous mixture of various epithelial and mesenchymal lineages. We use single-cell RNA sequencing and signaling lineage reporters to generate a spatial and transcriptional map of the lung mesenchyme. We find that each mesenchymal lineage has a distinct spatial address and transcriptional profile leading to unique niche regulatory functions. The mesenchymal alveolar niche cell is Wnt responsive, expresses Pdgfrα, and is critical for alveolar epithelial cell growth and self-renewal...
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28870601/lung-alveolar-repair-not-all-cells-are-equal
#6
Charlotte H Dean, Clare M Lloyd
The lungs are capable of repair but the extent to which this occurs varies widely. Recent data indicate that, following injury, different progenitor cell populations can arise, depending on the molecular environment. In turn, these result in either normal or aberrant alveolar repair. Thus, a key question in lung regenerative medicine is how to maintain a 'Goldilocks zone' of repair.
September 1, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28870520/loss-of-nrf2-promotes-alveolar-type-2-cell-loss-in-irradiated-fibrotic-lung
#7
Geri Traver, Stacey Mont, David Gius, William E Lawson, George X Ding, Konjeti R Sekhar, Michael L Freeman
The development of radiation-induced pulmonary fibrosis represents a critical clinical issue limiting delivery of therapeutic doses of radiation to non-small cell lung cancer. Identification of the cell types whose injury initiates a fibrotic response and the underlying biological factors that govern that response are needed for developing strategies that prevent or mitigate fibrosis. C57BL/6 mice (wild type, Nrf2 null, Nrf2(flox/flox), and Nrf2(Δ/Δ); SPC-Cre) were administered a thoracic dose of 12Gy and allowed to recover for 250 days...
September 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28860143/il-8-mediates-idiopathic-pulmonary-fibrosis-mesenchymal-progenitor-cell-fibrogenicity
#8
Libang Yang, Jeremy Herrera, Adam J Gilbertsen, Hong Xia, Karen Smith, Alexey Benyumov, Peter B Bitterman, Craig Alan Henke
Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrotic lung disease, but the mechanisms driving progression remain incompletely defined. We previously reported that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs), which serve as a cell-of-origin for IPF fibroblasts. Proliferating IPF MPCs are located at the periphery of fibroblastic foci in an active cellular front at the interface between the myofibroblast rich focus core and adjacent normal alveolar structures. Among a large set of genes that distinguish IPF MPCs from their control counterparts we identified IL-8 as a candidate mediator of IPF MPC fibrogenicity and driver of fibrotic progression...
August 31, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28855075/origin-and-production-of-inflammatory-perivascular-macrophages-in-pulmonary-hypertension
#9
REVIEW
Jonathan Florentin, Partha Dutta
Myeloid cells, including monocytes and macrophages participate in steady state immune homeostasis and help mount the adaptive immune response during infection. The function and production of these cells in sterile inflammation, such as pulmonary hypertension (PH), is understudied. Emerging data indicate that pulmonary inflammation mediated by lung perivascular macrophages is a key pathogenic driver of pulmonary remodeling leading to increased right ventricular systolic pressure (RVSP). However, the origin of these macrophages in pulmonary inflammation is unknown...
August 28, 2017: Cytokine
https://www.readbyqxmd.com/read/28854517/the-effect-of-meconium-exposure-on%C3%A2-the%C3%A2-expression-and-differentiation-of%C3%A2-amniotic-fluid-mesenchymal-stem-cells
#10
T J Jensen, J E Shui, C M Finck
BACKGROUND: The goal of this study was to determine if exposure to meconium would alter the phenotype of amniotic fluid mesenchymal stem cells (AF-MSCs) and the ability of these cells to be differentiated into distal airway type cells. METHODS: Meconium was collected, lyophilized and resuspended in PBS at 3 different concentrations (high, medium, and low). AF-MSCs were cultured in the presence of this meconium suspension for 8 hours and then analyzed for changes in gene expression...
August 23, 2017: Journal of Neonatal-perinatal Medicine
https://www.readbyqxmd.com/read/28842991/the-amniotic-fluid-as-a-source-of-mesenchymal-stem-cells-with-lung-specific-characteristics
#11
Flore Lesage, Silvia Zia, Julio Jiménez, Jan Deprest, Jaan Toelen
The amniotic fluid is a clinically accessible source of mesenchymal stem cells (AF-MSC) during gestation, which enables autologous cellular therapy for perinatal disorders. The origin of AF-MSC remains elusive: renal and neuronal progenitors have been isolated from the AF-MSC pool, yet no cells with pulmonary characteristics. We analyzed gene expression of pulmonary and renal markers of 212 clonal lines of AF-MSC isolated from amniocentesis samples. AF-MSC were cultured on dishes coated with extracellular matrix (ECM) proteins from decellularized fetal rabbit lungs...
August 26, 2017: Prenatal Diagnosis
https://www.readbyqxmd.com/read/28840018/the-role-of-bone-marrow-derived-endothelial-progenitor-cells-and-angiogenic-responses-in-chronic-obstructive-pulmonary-disease
#12
REVIEW
Brittany Salter, Roma Sehmi
Increased vascularity of the bronchial sub-mucosa is a cardinal feature of chronic obstructive pulmonary disease (COPD) and is associated with disease severity. Capillary engorgement, leakage, and vasodilatation can directly increase airway wall thickness resulting in airway luminal narrowing and facilitate inflammatory cell trafficking, thereby contributing to irreversible airflow obstruction, a characteristic of COPD. Airway wall neovascularisation, seen as increases in both the size and number of bronchial blood vessels is a prominent feature of COPD that correlates with reticular basement membrane thickening and airway obstruction...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28838957/vascular-endothelium-plays-a-key-role-in-directing-pulmonary-epithelial-cell-differentiation
#13
Jiayi Yao, Pierre J Guihard, Xiuju Wu, Ana M Blazquez-Medela, Melissa J Spencer, Medet Jumabay, Peter Tontonoz, Alan M Fogelman, Kristina I Boström, Yucheng Yao
The vascular endothelium is critical for induction of appropriate lineage differentiation in organogenesis. In this study, we report that dysfunctional pulmonary endothelium, resulting from the loss of matrix Gla protein (MGP), causes ectopic hepatic differentiation in the pulmonary epithelium. We demonstrate uncontrolled induction of the hepatic growth factor (HGF) caused by dysregulated cross talk between pulmonary endothelium and epithelium in Mgp-null lungs. Elevated HGF induced hepatocyte nuclear factor 4 α (Hnf4a), which competed with NK2 homeobox 1 (Nkx2...
August 24, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28836208/preparation-of-decellularized-lung-matrices-for-cell-culture-and-protein-analysis
#14
Franziska E Uhl, Darcy E Wagner, Daniel J Weiss
The limited available treatment options for patients with chronic lung diseases, such as fibrosis, lead to poor prognosis after diagnosis and short survival rates. An exciting new bioengineering approach utilizes de- and recellularization of lung tissue to potentially overcome donor organ shortage and immune reactions toward the received transplant. The goal of decellularization is to create a scaffold which contains the necessary framework for stability and functionality for regenerating lung tissue while removing immunomodulatory factors by removal of cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28821543/airway-basal-cell-heterogeneity-and-lung-squamous-cell-carcinoma
#15
EDITORIAL
Robert E Hynds, Sam M Janes
Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution...
August 18, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28806170/tips-from-the-embryonic-lung
#16
Avinash Waghray, Jayaraj Rajagopal
A new source of progenitor cells can now be used to study hidden aspects of human lung development and pediatric lung disease.
August 14, 2017: ELife
https://www.readbyqxmd.com/read/28805015/stromelysin-2-mmp-10-a-novel-mediator-of-vascular-remodeling-underlying-pulmonary-hypertension-associated-with-systemic-sclerosis
#17
Jérôme Avouac, Christophe Guignabert, Anna Maria Hoffmann-Vold, Barbara Ruiz, Peter Dorfmuller, Sonia Pezet, Olivia Amar, Ly Tu, Jérôme Van Wassenhove, Jérémy Sadoine, David Launay, Muriel Elhai, Anne Cauvet, Arun Subramaniam, Robert Resnick, Eric Hachulla, Øyvind Molberg, André Kahan, Marc Humbert, Yannick Allanore
OBJECTIVE: To decipher the role of gene candidates involved in pulmonary hypertension (PH) associated with systemic sclerosis (SSc). METHODS: Gene candidates were identified through microarray experiments performed on Affymetrix GeneChip(®) Human Exon 1.0 ST Arrays in endothelial progenitor cell (EPC)-derived endothelial cells (ECs) issued from patients with SSc-PH, SSc without PH and controls. Expression of identified candidates was assessed by quantitative sandwich ELISA in the serum and by immunohistochemistry in lesional lung tissue...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28802115/production-of-high-purity-alveolar-like-cells-from-ipscs-through-depletion-of-uncommitted-cells-after-afe-induction
#18
Adam Mitchell, Charles T Drinnan, Todd Jensen, Christine Finck
Protocols to differentiate induced pluripotent stem cells (iPSCs) into specialized cells are continually evolving. iPSCs can be differentiated to alveolar cells with protocols that focus on development, specifically by inducing differentiation into definitive endoderm (DE), anterior foregut endoderm (AFE) and then lung bud progenitor intermediaries. However, current protocols result in a relatively low yield of the desired alveolar cells. The aim of this study was to evaluate whether depleting uncommitted cells after AFE induction would have a beneficial effect on alveolar cell yield...
August 3, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28799208/ccr2-monocytic-myeloid-derived-immunosuppressive-cells-m-mdsc-inhibit-collagen-degradation-and-promote-lung-fibrosis-by-producing-tgf-%C3%AE-1
#19
Astrid Lebrun, Sandra Lo Re, Mathilde Chantry, Xavier Izquierdo Carerra, Francine Uwambayinema, Doriana Ricci, Raynal Devosse, Saloua Ibouraadaten, Lisa Brombin, Mihaly Palmai-Pallag, Yousof Yakoub, Manolis Pasparakis, Dominique Lison, François Huaux
Monocytes infiltrating scar tissue are predominantly viewed as progenitor cells. Here, we show that tissue CCR2(+) monocytes possess specific immunosuppressive and pro-fibrotic functions. CCR2(+) monocytic cells are acutely recruited to the lung before the onset of silica-induced fibrosis in mice. These tissue monocytes are defined as monocytic-Myeloid-Derived Suppressor Cells (M-MDSC) because they significantly suppress T lymphocyte proliferation in vitro. M-MDSC collected from silica-treated mice also express TGF-β1, which stimulates lung fibroblasts to release TIMP-1, an inhibitor of metalloproteinase collagenolytic activity...
August 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28783171/the-pdgfr%C3%AE-laminin-b1-keratin-19-cascade-drives-tumor-progression-at-the-invasive-front-of-human-hepatocellular-carcinoma
#20
O Govaere, M Petz, J Wouters, Y-P Vandewynckel, E J Scott, B Topal, F Nevens, C Verslype, Q M Anstee, H Van Vlierberghe, W Mikulits, T Roskams
Human hepatocellular carcinomas (HCCs) expressing the biliary/hepatic progenitor cell marker keratin 19 (K19) have been linked with a poor prognosis and exhibit an increase in platelet-derived growth factor receptor α (PDGFRα) and laminin beta 1 (LAMB1) expression. PDGFRα has been reported to induce de novo synthesis of LAMB1 protein in a Sjogren syndrome antigen B (La/SSB)-dependent manner in a murine metastasis model. However, the role of this cascade in human HCC remains unclear. This study focused on the functional role of the PDGFRα-La/SSB-LAMB1 pathway and its molecular link to K19 expression in human HCC...
August 7, 2017: Oncogene
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