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Lung progenitor

Bingqing Xie, Bharathi Laxman, Somaye Hashemifar, Randi Stern, T Conrad Gilliam, Natalia Maltsev, Steven R White
Basal airway epithelial cells (AEC) constitute stem/progenitor cells within the central airways and respond to mucosal injury in an ordered sequence of spreading, migration, proliferation, and differentiation to needed cell types. However, dynamic gene transcription in the early events after mucosal injury has not been studied in AEC. We examined gene expression using microarrays following mechanical injury (MI) in primary human AEC grown in submersion culture to generate basal cells and in the air-liquid interface to generate differentiated AEC (dAEC) that include goblet and ciliated cells...
2018: PloS One
Ruhang Tang, Liufang Jing, Vincent P Willard, Chia-Lung Wu, Farshid Guilak, Jun Chen, Lori A Setton
BACKGROUND: Intervertebral disc (IVD) degeneration is characterized by an early decrease in cellularity of the nucleus pulposus (NP) region, and associated extracellular matrix changes, reduced hydration, and progressive degeneration. Cell-based IVD therapy has emerged as an area of great interest, with studies reporting regenerative potential for many cell sources, including autologous or allogeneic chondrocytes, primary IVD cells, and stem cells. Few approaches, however, have clear strategies to promote the NP phenotype, in part due to a limited knowledge of the defined markers and differentiation protocols for this lineage...
March 9, 2018: Stem Cell Research & Therapy
Satoshi Ikeda, Terufumi Kato, Takashi Ogura, Akimasa Sekine, Tsuneyuki Oda, Noriyuki Masuda, Satoshi Igawa, Ken Katono, Sakiko Otani, Kouzo Yamada, Haruhiro Saito, Tetsuro Kondo, Yukio Hosomi, Yoshiro Nakahara, Masanori Nishikawa, Keiko Utumi, Yuki Misumi, Takeharu Yamanaka, Kentaro Sakamaki, Hiroaki Okamoto
BACKGROUND: Preclinical studies have demonstrated that docetaxel and bevacizumab may act synergistically by decreasing endothelial cell proliferation and preventing circulating endothelial progenitor mobilization. The objective of this study was to assess the efficacy and safety of a combination therapy of bevacizumab, cisplatin, and docetaxel in chemotherapy-naive Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS: Eligible patients were chemotherapy-naive and had advanced/recurrent non-squamous NSCLC...
March 2, 2018: BMC Cancer
Ye Wei, Fangzheng Zhou, Haibo Zhou, Jing Huang, Dandan Yu, Gang Wu
To supply tumor tissues with nutrients and oxygen, endothelial progenitor cells (EPCs) home to tumor sites and contribute to neovascularization. Although the precise mechanism of EPCs-induced neovascularization remains poorly understood in non-small cell lung cancer (NSCLC), histone deacetylase 7 (HDAC7) is considered as a critical regulator. To explore the function of HDAC7 in neovascularization induced by EPCs, tube formation assay, immunofluorescence, microarray, Western blot analysis and animal models were performed...
February 28, 2018: International Journal of Cancer. Journal International du Cancer
William J Zacharias, David B Frank, Jarod A Zepp, Michael P Morley, Farrah A Alkhaleel, Jun Kong, Su Zhou, Edward Cantu, Edward E Morrisey
Functional tissue regeneration is required for the restoration of normal organ homeostasis after severe injury. Some organs, such as the intestine, harbour active stem cells throughout homeostasis and regeneration; more quiescent organs, such as the lung, often contain facultative progenitor cells that are recruited after injury to participate in regeneration. Here we show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the alveolar type 2 cell population acts as a major facultative progenitor cell in the distal lung...
February 28, 2018: Nature
Kalina Paunovska, Cory D Sago, Christopher M Monaco, William H Hudson, Marielena Gamboa Castro, Tobi G Rudoltz, Sujay Kalathoor, Daryll A Vanover, Philip J Santangelo, Rafi Ahmed, Anton V Bryskin, James Dahlman
Endothelial cells and macrophages play active roles in disease, and as a result, are important targets for nucleic acid therapies. While thousands of chemically distinct lipid nanoparticles (LNPs) can be synthesized to deliver nucleic acids, studying more than a few LNPs in vivo is challenging. As a result, it is difficult to understand how nanoparticles target these cells in vivo. Using high throughput LNP barcoding, we quantified how well LNPs delivered DNA barcodes to endothelial cells and macrophages in vitro, as well as endothelial cells and macrophages isolated from the lung, heart, and bone marrow in vivo...
February 28, 2018: Nano Letters
Takaaki Ogoshi, Masato Tsutsui, Takashi Kido, Mayuko Sakanashi, Keisuke Naito, Keishi Oda, Hiroshi Ishimoto, Sohsuke Yamada, Ke-Yong Wang, Yumiko Toyohira, Hiroto Izumi, Hiroaki Masuzaki, Hiroaki Shimokawa, Nobuyuki Yanagihara, Kazuhiro Yatera, Hiroshi Mukae
RATIONALE: Nitric oxide (NO), synthesized by NO synthases (NOSs), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive. OBJECTIVES: To determine the role of NOSs in BM cells in PH. METHODS: Experiments were performed on 36 patients with idiopathic pulmonary fibrosis, and on wild-type (WT), neuronal (nNOS), inducible (iNOS), endothelial NOS (eNOS)-/-, and n/i/eNOSs-/- mice...
February 26, 2018: American Journal of Respiratory and Critical Care Medicine
Tyler J Loftus, Kolenkode B Kannan, Christy S Carter, Jessica M Plazas, Juan C Mira, Scott C Brakenridge, Christiaan Leeuwenburgh, Philip A Efron, Alicia M Mohr
BACKGROUND: Hypercatecholaminemia and bone marrow dysfunction have been implicated in the pathophysiology of persistent injury-associated anemia. The elderly may be more vulnerable to bone marrow dysfunction due to high basal and peak catecholamine levels and impaired hematopoietic progenitor growth. We hypothesized that aging would adversely affect persistent injury-associated anemia. METHODS: Male Sprague-Dawley rats aged 8 to 9 weeks and F344-BN rats aged 25 months were randomized to naive controls, lung contusion plus hemorrhagic shock (LCHS), and LCHS plus daily chronic restraint stress (LCHS/CS)...
March 2018: Journal of Trauma and Acute Care Surgery
X Tan, F-J Shao, G-J Fan, Y-T Ying
Plexiform lesions are characteristic histological changes of pulmonary arteries in human patients with severe pulmonary arterial hypertension (PAH) and are regarded as angiogenic lesions. Meat-type broiler chickens are susceptible to PAH and can develop plexiform lesions spontaneously. Whether the lesion development in broilers is associated with PAH predisposition and lung angiogenic environment remains unclear. Moreover, little is known about the cellular origin of these structures. In this work, plexiform lesions were detected in both layer chickens (a strain known to be resistant to PAH) and broiler chickens aged between 1 and 6 wk with normal pulmonary arterial pressures...
February 14, 2018: Poultry Science
Wei Tang, Steven G Smith, Wei Du, Akash Gugilla, Juan Du, John Paul Oliveria, Karen Howie, Brittany M Salter, Gail M Gauvreau, Paul M O'Byrne, Roma Sehmi
Background: Eosinophil-lineage committed progenitor cells (EoP) migrate from the bone marrow and differentiate locally to provide an ongoing source of mature eosinophils in asthmatic inflammatory responses in the airways. Sputum levels of EoP are increased in asthmatics compared to normal controls suggesting an exaggerated eosinophilopoietic environment in the airways. Understanding what factors promote EoP traffic to the airways is important to understand the diathesis of asthma pathology...
2018: Clinical and Translational Allergy
Edwin J Ostrin, Danielle R Little, Kamryn N Gerner-Mauro, Elizabeth A Sumner, Ricardo Ríos-Corzo, Elizabeth Ambrosio, Samantha E Holt, Nicolas R Forcioli-Conti, Haruhiko Akiyama, Sam M Hanash, Shioko Kimura, Sarah X L Huang, Jichao Chen
The entire lung epithelium arises from SOX9 (SRY box 9)-expressing progenitors that form the respiratory tree and differentiate into airway and alveolar cells. Despite progress in understanding their initial specification within the embryonic foregut, how these progenitors are subsequently maintained is less clear. Using inducible, progenitor-specific genetic mosaic mouse models, we show that beta-Catenin (CTNNB1) maintains the lung progenitors by promoting a hierarchical lung progenitor gene signature, suppressing gastrointestinal (GI) genes, and regulating NKX2...
February 13, 2018: Development
Peter Afdal, Antoine F AbdelMassih
Severe angio-obliterative pulmonary vascular disease (PAH) remains a disease characterized by great morbidity and shortened survival. Unfortunately, the only currently available treatments for angio-obliterative changes are palliative in the form of pulmonary vasodilators evolving from the phosphodiesterase inhibitor sildenafil to endothelin receptor antagonist: Bosentan; while the only definitive treatment is lung transplantation which remains dependent on the availability of donors and the transplant policies which vary widely from a country to another...
February 12, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Ji-Ae Kim, Rak-Kyun Seong, Mukesh Kumar, Ok Sarah Shin
Zika virus (ZIKV) has recently emerged as a new public health threat. ZIKV infections have caused a wide spectrum of neurological diseases, such as Guillain-Barré syndrome, myelitis, meningoencephalitis, and congenital microcephaly. No effective therapies currently exist for treating patients infected with ZIKV. Herein, we evaluated the anti-viral activity of favipiravir (T-705) and ribavirin against Asian and African strains of ZIKV using different cell models, including human neuronal progenitor cells (hNPCs), human dermal fibroblasts (HDFs), human lung adenocarcinoma cells (A549) and Vero cells...
February 9, 2018: Viruses
Ahmad Nabhan, Douglas G Brownfield, Pehr B Harbury, Mark A Krasnow, Tushar J Desai
Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat AT1 cells, which mediate gas exchange, and AT2 cells, which secret surfactant. Rare AT2s also function as alveolar stem cells. We show that AT2 lung stem cells display active Wnt signaling and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depletes these stem cells. Daughter cells leaving the Wnt niche transdifferentiate into AT1s: maintaining Wnt signaling prevents transdifferentiation whereas abrogating Wnt signaling promotes it...
February 1, 2018: Science
Jiao Li, Zheng Wang, Qiqi Chu, Kewu Jiang, Juan Li, Nan Tang
The differentiation of alveolar epithelial type I (AT1) and type II (AT2) cells is essential for the lung gas exchange function. Disruption of this process results in neonatal death or in severe lung diseases that last into adulthood. We developed live imaging techniques to characterize the mechanisms that control alveolar epithelial cell differentiation. We discovered that mechanical forces generated from the inhalation of amniotic fluid by fetal breathing movements are essential for AT1 cell differentiation...
February 5, 2018: Developmental Cell
Beiyun Zhou, Per Flodby, Jiao Luo, Dan R Castillo, Yixin Liu, Fa-Xing Yu, Alicia McConnell, Bino Varghese, Guanglei Li, Nyam-Osor Chimge, Mitsuhiro Sunohara, Michael N Koss, Wafaa Elatre, Peter Conti, Janice M Liebler, Chenchen Yang, Crystal N Marconett, Ite A Laird-Offringa, Parviz Minoo, Kunliang Guan, Barry R Stripp, Edward D Crandall, Zea Borok
Claudins, the integral tight junction (TJ) proteins that regulate paracellular permeability and cell polarity, are frequently dysregulated in cancer; however, their role in neoplastic progression is unclear. Here, we demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II (AT2) cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice...
February 5, 2018: Journal of Clinical Investigation
W Samuel Fagg, Naiyou Liu, Ming-Jim Yang, Ke Cheng, Eric Chung, Jae-Sung Kim, Gordon Wu, Jeffrey Fair
Attaining consistent robust engraftment in the structurally normal liver is an obstacle for cellular transplantation. Most experimental approaches to increase transplanted cells' engraftment involve recipient-centered deleterious methods such as partial hepatectomy or irradiation which may be unsuitable in the clinic. Here, we present a cell-based strategy that increases engraftment into the structurally normal liver using a combination of magnetic targeting and proliferative endoderm progenitor (EPs) cells...
December 2017: Cell Transplantation
David Michael Habiel, Milena Sobral Espindola, Ana Lucia Coelho, Cory Michel Hogaboam
Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease of unknown etiopathogenesis with limited therapeutic options. IPF is characterized by an abundance of fibroblasts and loss of epithelial progenitors, which cumulates in unrelenting fibrotic lung remodeling and loss of normal oxygenation. IPF has been challenging to model in rodents; nonetheless, mouse models of lung fibrosis provide clues as to the natural progression of lung injury and remodeling, but many have not been useful in predicting efficacy of therapeutics in clinical IPF...
January 25, 2018: American Journal of Pathology
Marissa J Schafer, Andrew J Haak, Daniel J Tschumperlin, Nathan K LeBrasseur
PURPOSE OF THE REVIEW: Senescent cells have the capacity to both effect and limit fibrosis. Senotherapeutics target senescent cells to improve aging conditions. Here, we review the contexts in which senescent cells mediate wound healing and fibrotic pathology and the potential utility of senotherapeutic drugs for treatment of fibrotic disease. RECENT FINDINGS: Multi-action and temporal considerations influence deleterious versus beneficial actions of senescent cells...
January 26, 2018: Current Rheumatology Reports
Natalia F Smirnova, Oliver Eickelberg
No abstract text is available yet for this article.
January 19, 2018: American Journal of Respiratory and Critical Care Medicine
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