Progenitor cells of the distal lung and their potential role in neonatal lung disease

2014 ◽  
Vol 100 (3) ◽  
pp. 217-226 ◽  
Author(s):  
Jennifer J.P. Collins ◽  
Bernard Thébaud
Keyword(s):  
Lung Disease ◽  
Progenitor Cells ◽  
Potential Role ◽  
Neonatal Lung ◽  
Distal Lung

scholarly journals SAT0014 ENDOTHELIAL PROGENITOR CELLS: ROLE IN ENDOTHELIAL DAMAGE OF INTERSTITIAL LUNG DISEASE ASSOCIATED TO RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 937.1-937
Author(s):  
V. Pulito-Cueto ◽  
S. Remuzgo-Martínez ◽  
F. Genre ◽  
V. M. Mora-Cuesta ◽  
D. Iturbe Fernández ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Potential Role ◽  
Endothelial Damage ◽  
Research Support ◽  
Endothelial Progenitor

Background:Interstitial lung disease (ILD) is one of the most significant comorbidities of rheumatoid arthritis (RA), increasing the mortality in these patients [1,2]. Although the pathogenesis of ILD associated to RA (RA-ILD+) remains poorly defined [1], it is known that vascular tissue plays a crucial role in lung physiology [3]. In this context, a population of cells termed endothelial progenitor cells (EPC) are involved in vasculogenesis and endothelial tissue repair [4]. Previous reports suggest the implication of EPC in different conditions such as RA and idiopathic pulmonary fibrosis (IPF), the most common and destructive ILD [5,6]. Nevertheless, little is known about their specific role in RA-ILD+.Objectives:The purpose of this study was to shed light on the potential role of EPC in endothelial damage in RA-ILD+.Methods:Peripheral venous blood was collected from a total of 68 individuals (18 with RA-ILD+, 17 with RA-ILD-, 19 with IPF and 14 healthy controls). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of EPC was analyzed by the expression of surface antigens by flow cytometry. The combination of antibodies against the stem cell marker CD34, the immature progenitor marker CD133, the endothelial marker VEGF receptor 2 (CD309) and the common leukocyte antigen CD45 was used. EPC were considered as CD34+, CD45Low, CD309+and CD133+. All statistical analyses were performed using Prism software 5 (GraphPad).Results:EPC frequency was significantly increased in patients with RA-ILD+, RA-ILD-and IPF compared to controls (p=0.001, p=0.002, p< 0.0001, respectively). Nevertheless, patients with RA, both RA-ILD+and RA-ILD-, showed a lower frequency of EPC than those with IPF (p= 0.048, p= 0.006, respectively).Conclusion:Our results provide evidence for a potential role of EPC as a reparative compensatory mechanism related to endothelial damage in RA-ILD+, RA-ILD-and IPF patients. Interestingly, EPC frequency may help to establish a differential diagnostic between patients with IPF and those who have an underlying autoimmune disease (RA-ILD+).References:[1] J Clin Med 2019; 8: 2038;[2] Arthritis Rheumatol 2015; 67: 28-38;[3] Nat Protoc 2015; 10: 1697-1708;[4] Science 1997; 275: 964-966;[5] Rheumatology (Oxford) 2012; 51: 1775-1784;[6] Angiogenesis 2013; 16: 147-157.Acknowledgments:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: PI18/00042 (ISCIII-ERDF); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo-Martínez: None declared, Fernanda Genre: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, Sonia Fernández-Rozas: None declared, Leticia Lera-Gómez: None declared, Pilar Alonso Lecue: None declared, Javier Rodriguez Carrio: None declared, Belén Atienza-Mateo: None declared, Virginia Portilla: None declared, David Merino: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD, Alfonso Corrales Speakers bureau: Abbvie, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

scholarly journals Transduction of Pig Small Airway Epithelial Cells and Distal Lung Progenitor Cells by AAV4

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1014
Author(s):  
Oliver G. Chen ◽  
Steven E. Mather ◽  
Christian M. Brommel ◽  
Bradley A. Hamilton ◽  
Annie Ehler ◽  
...  
Keyword(s):  
Lung Disease ◽  
Progenitor Cells ◽  
Targeted Delivery ◽  
Bacterial Colonization ◽  
Small Airway ◽  
Large Animal ◽  
Small Airways ◽  
Airway Epithelia ◽  
Distal Lung ◽  
Lung Progenitor

Cystic fibrosis (CF) is caused by genetic mutations of the CF transmembrane conductance regulator (CFTR), leading to disrupted transport of Cl− and bicarbonate and CF lung disease featuring bacterial colonization and chronic infection in conducting airways. CF pigs engineered by mutating CFTR develop lung disease that mimics human CF, and are well-suited for investigating CF lung disease therapeutics. Clinical data suggest small airways play a key role in the early pathogenesis of CF lung disease, but few preclinical studies have focused on small airways. Efficient targeted delivery of CFTR cDNA to small airway epithelium may correct the CFTR defect and prevent lung infections. Adeno-associated virus 4 (AAV4) is a natural AAV serotype and a safe vector with lower immunogenicity than other gene therapy vectors such as adenovirus. Our analysis of AAV natural serotypes using cultured primary pig airway epithelia showed that AAV4 has high tropism for airway epithelia and higher transduction efficiency for small airways compared with large airways. AAV4 mediated the delivery of CFTR, and corrected Cl− transport in cultured primary small airway epithelia from CF pigs. Moreover, AAV4 was superior to all other natural AAV serotypes in transducing ITGα6β4+ pig distal lung progenitor cells. In addition, AAV4 encoding eGFP can infect pig distal lung epithelia in vivo. This study demonstrates AAV4 tropism in small airway progenitor cells, which it efficiently transduces. AAV4 offers a novel tool for mechanistical study of the role of small airway in CF lung pathogenesis in a preclinical large animal model.

scholarly journals AB0094 INCREASE OF ENDOTHELIAL PROGENITOR CELLS IN SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1076.1-1076
Author(s):  
V. Pulito-Cueto ◽  
S. Remuzgo Martinez ◽  
F. Genre ◽  
B. Atienza-Mateo ◽  
V. M. Mora-Cuesta ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Potential Role ◽  
Type I ◽  
Research Support ◽  
Endothelial Progenitor

Background:Endothelial progenitor cells (EPC), involved in vasculogenesis and endothelial tissue repair, have been described as relevant players in vascular and connective tissue diseases [1-2]. In this regard, a previous study of our group disclosed that the degree of EPC frequency may help to identify the presence of interstitial lung disease (ILD) in rheumatoid arthritis patients [3]. Given that ILD is the main cause of mortality in patients with systemic sclerosis (SSc) [1, 4-6], the understanding of the role of EPC in the mechanism of SSc-ILD+ vasculopathy is crucial.Objectives:To assess the potential role of EPC on vascular dysfunction associated with the presence of ILD in patients with SSc.Methods:Peripheral venous blood was collected from a total of 39 patients with SSc, 20 with ILD (SSc-ILD+) and 19 without ILD (SSc-ILD-). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of EPC was analyzed by flow cytometry. EPC were considered as CD34+, CD45Low, CD309+ and CD133+.Results:Statistically significant differences in EPC frequency between patients with SSc-ILD+ and patients with SSc-ILD- were disclosed. Specifically, an increase of EPC frequency was observed in SSc-ILD+ patients when compared to patients with SSc-ILD- (mean ± standard deviation: 0.033 ± 0.012 versus 0.021 ± 0.017, respectively, p=0.012).Conclusion:Our results suggest a potential role of EPC on vascular damage associated with the manifestation of ILD in patients with SSc.References:[1]Eur J Rheumatol 2020;7(Suppl 3):S139-S146.[2]Arthritis Rheum 2009;60(11):3168-79.[3]J Clin Med 2020;9(12):4098.[4]Ann Rheum Dis 2007;66(7):940-4.[5]Rheumatology (Oxford) 2010;49(12):2375-80.[6]Eur Respir Rev 2015;24(135):102-14.Acknowledgements:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: INNVAL20/06 (IDIVAL); RP-F: START PROJECT (FOREUM); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Belén Atienza-Mateo: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe-Fernández: None declared, Leticia Lera-Gómez: None declared, Raquel Pérez-Fernández: None declared, Diana Prieto-Peña: None declared, Virginia Portilla: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Alfonso Corrales: None declared, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Speakers bureau: Pfizer, Abbvie, MSD, Grant/research support from: Pfizer, Abbvie, MSD

scholarly journals Predictors of home oxygen duration in chronic neonatal lung disease

2021 ◽  
Vol 56 (5) ◽  
pp. 992-999
Author(s):  
Matthew D. Wong ◽  
Melissa Neylan ◽  
Gordon Williams ◽  
Syeda F. Zahir ◽  
Jasneek Chawla
Keyword(s):  
Lung Disease ◽  
Neonatal Lung ◽  
Chronic Neonatal Lung Disease

scholarly journals Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures

2020 ◽  
Author(s):  
Ameen A. Salahudeen ◽  
Shannon S. Choi ◽  
Arjun Rustagi ◽  
Junjie Zhu ◽  
Sean M. de la O ◽  
...  
Keyword(s):  
Lung Disease ◽  
Single Cell ◽  
Basal Cell ◽  
Human Lung ◽  
Basal Cells ◽  
Ciliated Cells ◽  
Club Cells ◽  
Distal Lung

ABSTRACTThe distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human distal lung stem cell identification has been impaired by quiescence, anatomic divergence from mouse and lack of lineage tracing and clonogenic culture. Here, we developed robust feeder-free, chemically-defined culture of distal human lung progenitors as organoids derived clonally from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential, while basal cell organoids progressively developed lumens lined by differentiated club and ciliated cells. Organoids consisting solely of club cells were not observed. Upon single cell RNA-sequencing (scRNA-seq), alveolar organoids were composed of proliferative AT2 cells; however, basal organoid KRT5+ cells contained a distinct ITGA6+ITGB4+ mitotic population whose proliferation segregated to a TNFRSF12Ahi subfraction. Clonogenic organoid growth was markedly enriched within the TNFRSF12Ahi subset of FACS-purified ITGA6+ITGB4+ basal cells from human lung or derivative organoids. In vivo, TNFRSF12A+ cells comprised ~10% of KRT5+ basal cells and resided in clusters within terminal bronchioles. To model COVID-19 distal lung disease, we everted the polarity of basal and alveolar organoids to rapidly relocate differentiated club and ciliated cells from the organoid lumen to the exterior surface, thus displaying the SARS-CoV-2 receptor ACE2 on the outwardly-facing apical aspect. Accordingly, basal and AT2 “apical-out” organoids were infected by SARS-CoV-2, identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung alveolar and basal stem cells, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and exemplifies progenitor identification within a slowly proliferating human tissue. Further, our studies establish a facile in vitro organoid model for human distal lung infectious diseases including COVID-19-associated pneumonia.

Clubbing Due to Neonatal Lung Disease

1989 ◽  
Vol 78 (4) ◽  
pp. 631-632 ◽  
Author(s):  
D. E. Elder ◽  
N. R. C. Roberton
Keyword(s):  
Lung Disease ◽  
Neonatal Lung

scholarly journals Isolation and Characterization of Distal Lung Progenitor Cells

2012 ◽  
pp. 109-122 ◽  
Author(s):  
Barbara Driscoll ◽  
Alex Kikuchi ◽  
Allison N. Lau ◽  
Jooeun Lee ◽  
Raghava Reddy ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Isolation And Characterization ◽  
Distal Lung ◽  
Lung Progenitor

scholarly journals Exosomal miRNAs in Lung Diseases: From Biologic Function to Therapeutic Targets

2019 ◽  
Vol 8 (9) ◽  
pp. 1345 ◽  
Author(s):  
Julien Guiot ◽  
Ingrid Struman ◽  
Edouard Louis ◽  
Renaud Louis ◽  
Michel Malaise ◽  
...  
Keyword(s):  
Lung Disease ◽  
Disease Progression ◽  
Lung Diseases ◽  
Potential Role ◽  
Protective Effects ◽  
Diagnostic Biomarkers ◽  
Exosomal Mirnas ◽  
Stress Signals ◽  
Therapeutic Tools

Increasing evidence suggests the potential role of extracellular vesicles (EVs) in many lung diseases. According to their subcellular origin, secretion mechanism, and size, EVs are currently classified into three subpopulations: exosomes, microvesicles, and apoptotic bodies. Exosomes are released in most biofluids, including airway fluids, and play a key role in intercellular communication via the delivery of their cargo (e.g., microRNAs (miRNAs)) to target cell. In a physiological context, lung exosomes present protective effects against stress signals which allow them to participate in the maintenance of lung homeostasis. The presence of air pollution alters the composition of lung exosomes (dysregulation of exosomal miRNAs) and their homeostatic property. Indeed, besides their potential as diagnostic biomarkers for lung diseases, lung exosomes are functional units capable of dysregulating numerous pathophysiological processes (including inflammation or fibrosis), resulting in the promotion of lung disease progression. Here, we review recent studies on the known and potential role of lung exosomes/exosomal miRNAs, in the maintaining of lung homeostasis on one hand, and in promoting lung disease progression on the other. We will also discuss using exosomes as prognostic/diagnostic biomarkers as well as therapeutic tools for lung diseases.

Sign in / Sign up

Export Citation Format

Share Document