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Alveolar epithelial regeneration

Jiurong Liang, Yanli Zhang, Ting Xie, Ningshan Liu, Huaiyong Chen, Yan Geng, Adrianne Kurkciyan, Jessica Monterrosa Mena, Barry R Stripp, Dianhua Jiang, Paul W Noble
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...
October 3, 2016: Nature Medicine
Andrew James Paris, Yuhong Liu, Junjie Mei, Ning Dai, Lei Guo, Lynn Spruce, Kristin Hudock, Jacob Brenner, William Zacharias, Hankun Mei, April Slamowitz, Kartik Bhamidipati, Michael F Beers, Steven H Seeholzer, Edward E Morrisey, G Scott Worthen
Alveolar epithelial regeneration is essential for resolution of the acute respiratory distress syndrome (ARDS). Although neutrophils have traditionally been considered mediators of epithelial damage, recent studies suggest they promote type II pneumocyte (AT2) proliferation, which is essential for regenerating alveolar epithelium. These studies did not, however, evaluate this relationship in an in vivo model of alveolar epithelial repair following injury. To determine if neutrophils influence alveolar epithelial repair in vivo, we developed a unilateral acid injury model that creates a severe yet survivable injury with features similar to ARDS...
September 30, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Nasreen Akhtar, Weiping Li, Aleksander Mironov, Charles H Streuli
An important feature of the mammary gland is its ability to undergo repeated morphological changes during each reproductive cycle with profound tissue expansion in pregnancy and regression in involution. However, the mechanisms that determine the tissue's cyclic regenerative capacity remain elusive. We have now discovered that Cre-Lox ablation of Rac1 in mammary epithelia causes gross enlargement of the epithelial tree and defective alveolar regeneration in a second pregnancy. Architectural defects arise because loss of Rac1 disrupts clearance in involution following the first lactation...
September 12, 2016: Developmental Cell
Zeeshan Sheikh, Javairia Qureshi, Abdullah M Alshahrani, Heba Nassar, Yuichi Ikeda, Michael Glogauer, Bernhard Ganss
Certain cell populations within periodontal tissues possess the ability to induce regeneration, provided they have the opportunity to populate the wound or defect. Guided regeneration techniques have been investigated for regenerating periodontal tissues and such therapies usually utilize barrier membranes. Various natural and synthetic barrier membranes have been fabricated and tested to prevent epithelial and connective tissue cells from invading while allowing periodontal cells to selectively migrate into the defect...
September 9, 2016: Odontology
Yang Liu, Bi-Jie Jiang, Run-Zhen Zhao, Hong-Long Ji
Regeneration of the epithelium of mammalian lungs is essential for restoring normal function following injury, and various cells and mechanisms contribute to this regeneration and repair. Club cells, bronchioalveolar stem cells (BASCs), and alveolar type II epithelial cells (ATII) are dominant stem/progenitor cells for maintaining epithelial turnover and repair. Epithelial Na(+) channels (ENaC), a critical pathway for transapical salt and fluid transport, are expressed in lung epithelial progenitors, including club and ATII cells...
2016: International Journal of Biological Sciences
Zeeshan Sheikh, Abdul Samad Khan, Nima Roohpour, Michael Glogauer, Ihtesham U Rehman
Periodontal disease if left untreated can result in creation of defects within the alveolar ridge. Barrier membranes are frequently used with or without bone replacement graft materials for achieving periodontal guided tissue regeneration (GTR). Surface properties of barrier membranes play a vital role in their functionality and clinical success. In this study polyetherurethane (PEU) membranes were synthesized by using 4,4'-methylene-diphenyl diisocyanate (MDI), polytetramethylene oxide (PTMO) and 1,4-butane diol (BDO) as a chain extender via solution polymerization...
November 1, 2016: Materials Science & Engineering. C, Materials for Biological Applications
Salik Hussain, Zhaoxia Ji, Alexia J Taylor, Laura M DeGraff, Margaret George, Charles J Tucker, Chong Hyun Chang, Ruibin Li, James C Bonner, Stavros Garantziotis
Commercialization of multiwalled carbon nanotubes (MWCNT)-based applications has been hampered by concerns regarding their lung toxicity potential. Hyaluronic acid (HA) is a ubiquitously found polysaccharide, which is anti-inflammatory in its native high molecular weight form. HA-functionalized smart MWCNTs have shown promise as tumor-targeting drug delivery agents and can enhance bone repair and regeneration. However, it is unclear whether HA functionalization could reduce the pulmonary toxicity potential of MWCNTs...
August 23, 2016: ACS Nano
Po-Nien Tsao, Chisa Matsuoka, Shu-Chen Wei, Atsuyasu Sato, Susumu Sato, Koichi Hasegawa, Hung-Kuan Chen, Thai-Yen Ling, Munemasa Mori, Wellington V Cardoso, Mitsuru Morimoto
Abnormal enlargement of the alveolar spaces is a hallmark of conditions such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. Notch signaling is crucial for differentiation and regeneration and repair of the airway epithelium. However, how Notch influences the alveolar compartment and integrates this process with airway development remains little understood. Here we report a prominent role of Notch signaling in the epithelial-mesenchymal interactions that lead to alveolar formation in the developing lung...
July 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jennifer Quantius, Carole Schmoldt, Ana I Vazquez-Armendariz, Christin Becker, Elie El Agha, Jochen Wilhelm, Rory E Morty, István Vadász, Konstantin Mayer, Stefan Gattenloehner, Ludger Fink, Mikhail Matrosovich, Xiaokun Li, Werner Seeger, Juergen Lohmeyer, Saverio Bellusci, Susanne Herold
Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high...
June 2016: PLoS Pathogens
Michiko Horiguchi, Mai Hirokawa, Kaori Abe, Harumi Kumagai, Chikamasa Yamashita
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease with several causes, including smoking, and no curative therapeutic agent is available, particularly for destructive alveolar lesions. In this study, we investigated the differentiation-inducing effect on undifferentiated lung cells (Calu-6) and the alveolar regenerative effect of the active vitamin 1,25-dihydroxy vitamin D3 (VD3) with the ultimate goal of developing a novel curative drug for COPD. First, the differentiation-inducing effect of VD3 on Calu-6 cells was evaluated...
July 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Cho-Ming Chao, Alena Moiseenko, Klaus-Peter Zimmer, Saverio Bellusci
BACKGROUND: Alveologenesis is the last stage in lung development and is essential for building the gas-exchanging units called alveoli. Despite intensive lung research, the intricate crosstalk between mesenchymal and epithelial cell lineages during alveologenesis is poorly understood. This crosstalk contributes to the formation of the secondary septae, which are key structures of healthy alveoli. CONCLUSIONS: A better understanding of the cellular and molecular processes underlying the formation of the secondary septae is critical for the development of new therapies to protect or regenerate the alveoli...
December 2016: Molecular and Cellular Pediatrics
Zhongwei Cao, Raphael Lis, Michael Ginsberg, Deebly Chavez, Koji Shido, Sina Y Rabbany, Guo-Hua Fong, Thomas P Sakmar, Shahin Rafii, Bi-Sen Ding
Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages...
February 2016: Nature Medicine
Tian Yu, Ana Angelova Volponi, Rebecca Babb, Zhengwen An, Paul T Sharpe
Human teeth contain stem cells in all their mesenchymal-derived tissues, which include the pulp, periodontal ligament, and developing roots, in addition to the support tissues such as the alveolar bone. The precise roles of these cells remain poorly understood and most likely involve tissue repair mechanisms but their relative ease of harvesting makes teeth a valuable potential source of mesenchymal stem cells (MSCs) for therapeutic use. These dental MSC populations all appear to have the same developmental origins, being derived from cranial neural crest cells, a population of embryonic stem cells with multipotential properties...
2015: Current Topics in Developmental Biology
Kai-Chiang Yang, Yutaka Kitamura, Chang-Chin Wu, Hao-Hueng Chang, Thai-Yen Ling, Tzong-Fu Kuo
The purpose of this study was to demonstrate the feasibility of whole-tooth regeneration using a tooth germ-like construct. Dental pulp from upper incisors, canines, premolars, and molars were extracted from sexually mature miniature pigs. Pulp tissues were cultured and expanded in vitro to obtain dental pulp stem cells (DPSCs), and cells were differentiated into odontoblasts and osteoblasts. Epithelial cells were isolated from gingival epithelium. The epithelial cells, odontoblasts, and osteoblasts were seeded onto the surface, upper, and lower layers, respectively, of a bioactive scaffold...
April 2016: Artificial Organs
Masamitsu Oshima, Takashi Tsuji
Dental problems caused by dental caries, periodontal disease and tooth injury compromise the oral and general health issues. Current advances for the development of regenerative therapy have been influenced by our understanding of embryonic development, stem cell biology, and tissue engineering technology. Tooth regenerative therapy for tooth tissue repair and whole tooth replacement is currently expected a novel therapeutic concept with the full recovery of tooth physiological functions. Dental stem cells and cell-activating cytokines are thought to be candidate approach for tooth tissue regeneration because they have the potential to differentiate into tooth tissues in vitro and in vivo...
2015: Advances in Experimental Medicine and Biology
Takashi Kato, Kiyomasa Oka, Toshikazu Nakamura, Akihiko Ito
Lung alveolar regeneration occurs in adult human lungs as a result of proliferation, differentiation and alveolar morphogenesis of stem cells. It is increasingly being believed that bronchial epithelial cells (BECs) have a potential as stem cells, because they are potent to differentiate into multiple central and peripheral lung cell types in three-dimensional (3D) cultures, and they develop multiple foci with well-differentiated histogenesis after transformed into neoplastic cells. In this study, we investigated morphogenic abilities of HBE135 human BECs immortalized by E6/E7 oncogene in 3D cultures...
December 2015: Journal of Cellular and Molecular Medicine
Jenna Green, Mehari Endale, Herbert Auer, Anne-Karina T Perl
Epithelial-mesenchymal cell interactions and factors that control normal lung development are key players in lung injury, repair, and fibrosis. A number of studies have investigated the roles and sources of epithelial progenitors during lung regeneration; such information, however, is limited in lung fibroblasts. Thus, understanding the origin, phenotype, and roles of fibroblast progenitors in lung development, repair, and regeneration helps address these limitations. Using a combination of platelet-derived growth factor receptor α-green fluorescent protein (PDGFRα-GFP) reporter mice, microarray, real-time polymerase chain reaction, flow cytometry, and immunofluorescence, we characterized two distinct interstitial resident fibroblasts, myo- and matrix fibroblasts, and identified a role for PDGFRα kinase activity in regulating their activation during lung regeneration...
April 2016: American Journal of Respiratory Cell and Molecular Biology
Alban Girault, Jasmine Chebli, Anik Privé, Nguyen Thu Ngan Trinh, Emilie Maillé, Ryszard Grygorczyk, Emmanuelle Brochiero
BACKGROUND: Extensive alveolar epithelial injury and remodelling is a common feature of acute lung injury and acute respiratory distress syndrome (ARDS) and it has been established that epithelial regeneration, and secondary lung oedema resorption, is crucial for ARDS resolution. Much evidence indicates that K(+) channels are regulating epithelial repair processes; however, involvement of the KCa3.1 channels in alveolar repair has never been investigated before. RESULTS: Wound-healing assays demonstrated that the repair rates were increased in primary rat alveolar cell monolayers grown on a fibronectin matrix compared to non-coated supports, whereas an anti-β1-integrin antibody reduced it...
2015: Respiratory Research
Nevins W Todd, Sergei P Atamas, Irina G Luzina, Jeffrey R Galvin
Alveolar epithelial cell loss and impaired epithelial cell regeneration are currently accepted as central initiating events in idiopathic pulmonary fibrosis (IPF), but subsequent downstream effects remain uncertain. The most accepted downstream effect is aberrant and dysregulated mesenchymal cell proliferation and excess extracellular matrix (ECM) accumulation. However, biochemical and imaging studies have perhaps somewhat surprisingly indicated little increase in total lung collagen and lung tissue, and have rather shown a substantial decrease in lung aeration and lung air volume...
August 2015: Expert Review of Respiratory Medicine
Michiko Horiguchi, Yuki Oiso, Hitomi Sakai, Tomoki Motomura, Chikamasa Yamashita
Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease, causing widespread and irreversible alveoli collapse. The discovery of a low-molecular-weight compound that induces regeneration of pulmonary alveoli is of utmost urgency to cure intractable pulmonary diseases such as COPD. However, a practically useful compound for regenerating pulmonary alveoli is yet to be reported. Previously, we have elucidated that Akt phosphorylation is involved in a differentiation-inducing molecular mechanism of human alveolar epithelial stem cells, which play a role in regenerating pulmonary alveoli...
September 10, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
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