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Lung progenitor

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https://www.readbyqxmd.com/read/28546353/meeting-report-for-the-2017-national-institutes-of-health-national-heart-lung-and-blood-institute-progenitor-cell-biology-consortium-cardiovascular-bioengineering-workshop-and-symposium
#1
https://www.readbyqxmd.com/read/28538234/overview-of-lung-development-in-the-newborn-human
#2
David Warburton
In human neonates rapid adaptation from an aqueous intrauterine environment to permanent air breathing is the rate-limiting step for extrauterine life, failure of which justifies the existence of neonatal intensive care units. The lung develops at about 4-6 weeks' gestation in humans as a ventral outpouching of the primitive foregut into the surrounding ventral mesenchyme, termed the laryngotracheal groove. At its posterior end lie progenitor cells that form a pair of bronchial tubes, from which arise all the distal epithelial structures of the lung...
2017: Neonatology
https://www.readbyqxmd.com/read/28535533/malat1-modulates-tgf-%C3%AE-1-induced-endothelial-to-mesenchymal-transition-through-downregulation-of-mir-145
#3
Yin Xiang, Yachen Zhang, Yong Tang, Qianhui Li
BACKGROUND/AIMS: Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28530639/calcium-binding-protein-s100a4-confers-mesenchymal-progenitor-cell-fibrogenicity-in-idiopathic-pulmonary-fibrosis
#4
Hong Xia, Adam Gilbertsen, Jeremy Herrera, Emilian Racila, Karen Smith, Mark Peterson, Timothy Griffin, Alexey Benyumov, Libang Yang, Peter B Bitterman, Craig A Henke
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a prevalence of 1 million persons worldwide. The fibrosis spreads from affected alveoli into contiguous alveoli and leads to death by asphyxiation. We previously discovered that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs) that serve as a cell of origin for disease-mediating myofibroblasts. In a prior genomewide transcriptional analysis, we found that IPF MPCs displayed increased expression of S100 calcium-binding A4 (S100A4), a protein linked to cancer cell proliferation and invasiveness...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28530121/glucocorticoids-retain-bi-potent-fibroblast-progenitors-during-alveolar-septation-in-mice
#5
Stephen E McGowan, Diann M McCoy
Glucocorticoids have been widely used and exert pleiotropic effects on alveolar structure and function, but do not improve the long-term clinical outcomes for patients with bronchopulmonary dysplasia, emphysema, or interstitial lung diseases. Treatments which foster alveolar regeneration could substantially improve the long-term outcomes for such patients. One approach to alveolar regeneration is to stimulate and guide intrinsic alveolar progenitors along developmental pathways used during secondary septation...
May 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28501478/osr1-functions-downstream-of-hedgehog-pathway-to-regulate-foregut-development
#6
Lu Han, Jingyue Xu, Emily Grigg, Megan Slack, Praneet Chaturvedi, Rulang Jiang, Aaron M Zorn
During early fetal development, paracrine Hedgehog (HH) ligands secreted from the foregut epithelium activate Gli transcription factors in the surrounding mesenchyme to coordinate formation of the respiratory system, digestive track and the cardiovascular network. Although disruptions to this process can lead to devastating congenital defects, the underlying mechanisms and downstream targets, are poorly understood. We show that the zinc finger transcription factor Osr1 is a novel HH target as Osr1 expression in the foregut mesenchyme depends on HH signaling and the effector of HH pathway Gli3 binds to a conserved genomic loci near Osr1 promoter region...
May 10, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28501476/endothelial-cells-are-not-required-for-specification-of-respiratory-progenitors
#7
Jamie A Havrilak, Kristin R Melton, John M Shannon
Crosstalk between mesenchymal and epithelial cells influences organogenesis in multiple tissues, such as lung, pancreas, liver, and the nervous system. Lung mesenchyme comprises multiple cell types, however, and precise identification of the mesenchymal cell type(s) that drives early events in lung development remains unknown. Endothelial cells have been shown to be required for some aspects of lung epithelial patterning, lung stem cell differentiation, and regeneration after injury. Furthermore, endothelial cells are involved in early liver and pancreas development...
May 10, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28500076/stat5-is-required-for-cd103-dendritic-cell-and-alveolar-macrophage-development-and-protection-from-lung-injury
#8
William E Eddy, Ke-Qin Gong, Bryan Bell, William C Parks, Steven F Ziegler, Anne M Manicone
We tested the role of Stat5 in dendritic cell and alveolar macrophage (AM) homeostasis in the lung using CD11c-cre mediated deletion (Cre(+)5(f/f)). We show that Stat5 is required for CD103(+) dendritic cell and AM development. We found that fetal monocyte maturation into AMs was impaired in Cre(+)5(f/f) mice, and we also confirmed impaired AM development of progenitor cells using mixed chimera experiments. In the absence of Stat5 signaling in AMs, mice developed alveolar proteinosis with altered lipid homeostasis...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28484078/androgen-signaling-negatively-controls-group-2-innate-lymphoid-cells
#9
Sophie Laffont, Eve Blanquart, Magali Savignac, Claire Cénac, Gilles Laverny, Daniel Metzger, Jean-Philippe Girard, Gabrielle T Belz, Lucette Pelletier, Cyril Seillet, Jean-Charles Guéry
Prevalence of asthma is higher in women than in men, but the mechanisms underlying this sex bias are unknown. Group 2 innate lymphoid cells (ILC2s) are key regulators of type 2 inflammatory responses. Here, we show that ILC2 development is greatly influenced by male sex hormones. Male mice have reduced numbers of ILC2 progenitors (ILC2Ps) and mature ILC2s in peripheral tissues compared with females. In consequence, males exhibit reduced susceptibility to allergic airway inflammation in response to environmental allergens and less severe IL-33-driven lung inflammation, correlating with an impaired expansion of lung ILC2s...
May 8, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28474513/bone-marrow-endothelial-progenitor-cells-are-the-cellular-mediators-of-pulmonary-hypertension-in-the-murine-monocrotaline-injury-model
#10
Jason M Aliotta, Mandy Pereira, Sicheng Wen, Mark S Dooner, Michael Del Tatto, Elaine Papa, Yan Cheng, Laura Goldberg, Corey E Ventetuolo, Olin Liang, James R Klinger, Peter J Quesenberry
The role of bone marrow (BM) cells in modulating pulmonary hypertensive responses is not well understood. Determine if BM-derived endothelial progenitor cells (EPCs) induce pulmonary hypertension (PH) and if this is attenuated by mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). Three BM populations were studied: (a) BM from vehicle and monocrotaline (MCT)-treated mice (PH induction), (b) BM from vehicle-, MCT-treated mice that received MSC-EV infusion after vehicle, MCT treatment (PH reversal, in vivo), (c) BM from vehicle-, MCT-treated mice cultured with MSC-EVs (PH reversal, in vitro)...
May 5, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28473330/cd44-high-alveolar-type-ii-cells-show-stem-cell-properties-during-steady-state-alveolar-homeostasis
#11
Qian Chen, Varsha Suresh Kumar, Johanna Finn, Dianhua Jiang, Jiurong Liang, You-Yang Zhao, Yuru Liu
The alveolar epithelium is composed of type I cells covering most of the gas-blood exchange surface and type II cells secreting surfactant that lowers surface tension of alveoli to prevent alveolar collapse. Here we have identified a subgroup of type II cells expressing higher level of cell surface molecule CD44 (CD44high type II cells) that comprised ~3% of total type II cells in 5-10 week old mice. These cells were preferentially apposed to lung capillaries. They displayed a higher proliferation rate and augmented differentiation capacity into type I cells and the ability to form alveolar organoids compared to CD44low type II cells...
May 4, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28463231/disruption-of-lineage-specification-in-adult-pulmonary-mesenchymal-progenitor-cells-promotes-microvascular-dysfunction
#12
Christa F Gaskill, Erica J Carrier, Jonathan A Kropski, Nathaniel C Bloodworth, Swapna Menon, Robert F Foronjy, M Mark Taketo, Charles C Hong, Eric D Austin, James D West, Anna L Means, James E Loyd, W David Merryman, Anna R Hemnes, Stijn De Langhe, Timothy S Blackwell, Dwight J Klemm, Susan M Majka
Pulmonary vascular disease is characterized by remodeling and loss of microvessels and is typically attributed to pathological responses in vascular endothelium or abnormal smooth muscle cell phenotypes. We have challenged this understanding by defining an adult pulmonary mesenchymal progenitor cell (MPC) that regulates both microvascular function and angiogenesis. The current understanding of adult MPCs and their roles in homeostasis versus disease has been limited by a lack of genetic markers with which to lineage label multipotent mesenchyme and trace the differentiation of these MPCs into vascular lineages...
May 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28463226/prospective-isolation-of-nkx2-1-expressing-human-lung-progenitors-derived-from-pluripotent-stem-cells
#13
Finn Hawkins, Philipp Kramer, Anjali Jacob, Ian Driver, Dylan C Thomas, Katherine B McCauley, Nicholas Skvir, Ana M Crane, Anita A Kurmann, Anthony N Hollenberg, Sinead Nguyen, Brandon G Wong, Ahmad S Khalil, Sarah X L Huang, Susan Guttentag, Jason R Rock, John M Shannon, Brian R Davis, Darrell N Kotton
It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1-expressing (NKX2-1+) precursor cells. However, this hypothesis has not been formally tested owing to an inability to purify or track these progenitors for detailed characterization. Here we have engineered and developmentally differentiated NKX2-1GFP reporter pluripotent stem cells (PSCs) in vitro to generate and isolate human primordial lung progenitors that express NKX2-1 but are initially devoid of differentiated lung lineage markers...
May 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28459743/the-use-of-gmp-produced-bone-marrow-derived-stem-cells-in-combination-with-extracorporeal-membrane-oxygenation-in-ards-an-animal-model
#14
Ergin Kocyildirim, Nayra Cárdenes, Antony Ting, Eder Cáceres, Christian BermUdez, Mauricio Rojas
Acute respiratory distress syndrome (ARDS) is the result of a wide variety of disorders, which can be associated with different clinical disorders or systemic diseases directly affecting the lungs. Currently, the only existing therapy is limited to supportive care. In a 6 hour pilot study, we analyzed the use of the combination of both stem cell and extracorporeal membrane oxygenation (ECMO) strategies to prevent or treat severe lung injury. A total of 11 sheep were used. Five sheep received Escherichia coli endotoxin as a control group (group 1)...
May 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28459463/mycn-induces-neuroblastoma-in-primary-neural-crest-cells
#15
R R Olsen, J H Otero, J García-López, K Wallace, D Finkelstein, J E Rehg, Z Yin, Y-D Wang, K W Freeman
Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS), which causes 15% of pediatric cancer deaths. High-risk NBL is characterized by N-Myc amplification and segmental chromosomal gains and losses. Owing to limited disease models, the etiology of NBL is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying NBL based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9...
May 1, 2017: Oncogene
https://www.readbyqxmd.com/read/28452894/severe-trauma-and-chronic-stress-activates-extramedullary-erythropoiesis
#16
Ines G Alamo, Kolenkode B Kannan, Tyler J Loftus, Harry Ramos, Philip A Efron, Alicia M Mohr
BACKGROUND: Severe traumatic injury is associated with bone marrow dysfunction that manifests as impaired erythropoiesis and prolonged hematopoietic progenitor cell (HPC) mobilization from the bone marrow. Extramedullary erythropoiesis, the development of red blood cells outside the bone marrow, has not been studied following severe injury and critical illness. This study examined the influence of lung contusion/hemorrhagic shock (LCHS) followed by chronic stress (CS) on the rodent spleen and to investigate the involvement of the splenic erythropoietin/erythropoietin receptor and BMP4 signaling...
April 27, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28451462/pulmonary-adenocarcinoma-with-mucin-production-modulates-phenotype-according-to-common-genetic-traits-a-reappraisal-of-mucinous-adenocarcinoma-and-colloid-adenocarcinoma
#17
Angelica Sonzogni, Fabrizio Bianchi, Alessandra Fabbri, Mara Cossa, Giulio Rossi, Alberto Cavazza, Elena Tamborini, Federica Perrone, Adele Busico, Iolanda Capone, Benedetta Picciani, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi
Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA) of the lung represent separate tumour entities, or simply lie within a spectrum of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK-rearranged adenocarcinomas (ALKA), 8 non-mucinous KRAS-mutated adenocarcinomas (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX-2, MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin), neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone-related (oestrogen and progesterone receptors), pan-mucinous (HNF4A) and pan-epithelial (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS) for 50 recurrently altered cancer genes...
April 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28450224/pinocembrin-ex-vivo-preconditioning-improves-the-therapeutic-efficacy-of-endothelial-progenitor-cells-in-monocrotaline-induced-pulmonary-hypertension-in-rats
#18
Lamiaa A Ahmed, Sherine M Rizk, Shohda A El-Maraghy
Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). Endothelial progenitor cells was in vitro preconditioned with pinocembrin (25 mg/L) for 30 min before being i...
April 24, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28430622/serious-adverse-events-of-cell-therapy-for-respiratory-diseases-a-systematic-review-and-meta-analysis
#19
REVIEW
Runzhen Zhao, Zhenlei Su, Jing Wu, Hong-Long Ji
BACKGROUND: Cell therapy holds the most promising for acute and chronic deleterious respiratory diseases. However, the safety and tolerance for lung disorders are controversy. METHODS: We undertook a systematic review and meta-analyses of all 23 clinical studies of cell therapy. The outcomes were odds ratio (OR), risk difference (RD), Peto OR, relative risk, and mean difference of serious adverse events. RESULTS: 342 systemic infusions and 57 bronchial instillations (204 recipients) of cells were analyzed for acute respiratory distress syndrome (ARDS), bronchopulmonary dysplasia, pulmonary arterial hypertension, silicosis, sarcoidosis, extensively drug-resistant tuberculosis, chronic obstructive pulmonary diseases (COPD), and idiopathic pulmonary fibrosis...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423296/eltrombopag-added-to-standard-immunosuppression-for-aplastic-anemia
#20
Danielle M Townsley, Phillip Scheinberg, Thomas Winkler, Ronan Desmond, Bogdan Dumitriu, Olga Rios, Barbara Weinstein, Janet Valdez, Jennifer Lotter, Xingmin Feng, Marie Desierto, Harshraj Leuva, Margaret Bevans, Colin Wu, Andre Larochelle, Katherine R Calvo, Cynthia E Dunbar, Neal S Young
BACKGROUND: Acquired aplastic anemia results from immune-mediated destruction of bone marrow. Immunosuppressive therapies are effective, but reduced numbers of residual stem cells may limit their efficacy. In patients with aplastic anemia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist, led to clinically significant increases in blood counts in almost half the patients. We combined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe aplastic anemia...
April 20, 2017: New England Journal of Medicine
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