scholarly journals Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1602
Author(s):  
Tanya J. Bennet ◽  
Avineet Randhawa ◽  
Jessica Hua ◽  
Karen C. Cheung
Keyword(s):  
In Vitro Models ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Characterization Methods ◽  
Composition And Structure ◽  
Challenges And Opportunities ◽  
On Chip ◽  
Respiratory Conditions

The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.

scholarly journals Innovative In Vitro Models for the Study of Lung Diseases

2020 ◽  
Author(s):  
Vittorio Picchio ◽  
Vittoria Cammisotto ◽  
Francesca Pagano ◽  
Roberto Carnevale ◽  
Isotta Chimenti
Keyword(s):  
In Vitro Models ◽  
New Drugs ◽  
In Vivo Studies ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Physiological Relevance ◽  
Complex Models ◽  
On Chip

Basic and translational research on lung biology and pathology can greatly benefit from the development of 3D in vitro models with physiological relevance. Lung organoids and lungs-on-chip allow the creation of different kinds of in vitro microenvironments, that can be useful for the elucidation of novel pathogenetic pathways, for example concerning tissue fibrosis in chronic diseases. Moreover, they represent important translational models for the identification of novel therapeutic targets, and for preliminary testing of new drugs. In this chapter, we provide a selected overview of recent studies on innovative 3D in vitro models that have enhanced our knowledge on chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), particularly concerning oxidative stress and pro-fibrotic pathogenetic mechanisms. Despite several limitations, these complex models must be considered as complementary in all respects to in vivo studies on animal models and clinical research.

scholarly journals Extracellular Vesicles from Airway Secretions: New Insights in Lung Diseases

2021 ◽  
Vol 22 (2) ◽  
pp. 583
Author(s):  
Laura Pastor ◽  
Elisabeth Vera ◽  
Jose M. Marin ◽  
David Sanz-Rubio
Keyword(s):  
Extracellular Vesicles ◽  
Lung Diseases ◽  
Biomarker Discovery ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Lavage Fluid ◽  
In Vitro Models ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Lung diseases (LD) are one of the most common causes of death worldwide. Although it is known that chronic airway inflammation and excessive tissue repair are processes associated with LD such as asthma, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), their specific pathways remain unclear. Extracellular vesicles (EVs) are heterogeneous nanoscale membrane vesicles with an important role in cell-to-cell communication. EVs are present in general biofluids as plasma or urine but also in secretions of the airway as bronchoalveolar lavage fluid (BALF), induced sputum (IS), nasal lavage (NL) or pharyngeal lavage. Alterations of airway EV cargo could be crucial for understanding LD. Airway EVs have shown a role in the pathogenesis of some LD such as eosinophil increase in asthma, the promotion of lung cancer in vitro models in COPD and as biomarkers to distinguishing IPF in patients with diffuse lung diseases. In addition, they also have a promising future as therapeutics for LD. In this review, we focus on the importance of airway secretions in LD, the pivotal role of EVs from those secretions on their pathophysiology and their potential for biomarker discovery.

scholarly journals ILC2 Cells Promote Th2 Cell Differentiation in AECOPD Through Activated Notch-GATA3 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Jiang ◽  
Ren Cai ◽  
Jing Wang ◽  
Zheng Li ◽  
Dan Xu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Peripheral Blood ◽  
Culture Supernatant ◽  
Th2 Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Protein Levels ◽  
Th2 Cell

This study is to investigate the capacity of type 2 innate lymphoid cells (ILC2s) in regulating the Th2 type adaptive immune response of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The study enrolled healthy people, stable chronic obstructive pulmonary disease (COPD) patients, and AECOPD patients. Flow cytometry was used to detect Th2 and ILC2 cells in the peripheral blood. In addition, ILC2s from the peripheral blood of AECOPD patients were stimulated with PBS, IL-33, Jagged1, DAPT, IL-33+Jagged1, IL-33+DAPT, and IL-33+Jagged-1+DAP in vitro. The levels of cytokines in the culture supernatant were detected by ELISA and the culture supernatant was used to culture CD4 + T cells. The mRNA and protein levels of Notch1, hes1, GATA3, RORα, and NF-κB of ILC2s were detected by real-time PCR and Western blot. The proportion of Th2 and ILC2s was significantly increased in the peripheral blood of AECOPD patients, alone with the increased Notch1, hes1, and GATA3 mRNA levels. In vitro results showed that the mRNA and protein levels of Notch1, hes1, GATA3 and NF-κB were significantly increased after stimulation with Notch agonist, meanwhile, the level of type 2 cytokines were increased in the supernatant of cells stimulated with Notch agonist, and significantly promoted differentiation of Th2 cells in vitro. Disruption of Notch pathway weakened GATA3 expression and cytokine production, and ultimately affected the differentiation of Th2 cells. In conclusion, our results suggest that ILC2s can promote Th2 cell differentiation in AECOPD via activated Notch-GATA3 signal pathway.

scholarly journals Possible Implication of Hypoxia-mediated Incomplete Neutrophil Extracellular Trap Formation in Pneumonia-induced Exacerbation of Lung Diseases

2021 ◽  
Author(s):  
Sakiko Masuda ◽  
Kurumi Kato ◽  
Misato Ishibashi ◽  
Yuka Nishibata ◽  
Ayako Sugimoto ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Actin Polymerization ◽  
Hypoxia Inducible Factor ◽  
Neutrophil Extracellular Trap ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Hypoxic Conditions ◽  
Pulmonary Arterial ◽  
Underlying Diseases

Abstract When patients with preexisting lung diseases, such as chronic obstructive pulmonary disease, interstitial pneumonitis, and pulmonary arterial hypertension, develop pneumonia, the complication often exacerbates the underlying diseases. Although neutrophil extracellular traps (NETs) are important components of innate immune system, the residue of NETs in the tissue can harm the host. We examined the expression of hypoxia-inducible factor 1α (HIF-1α) and NETs in the lungs of patients with lung diseases complicated with pneumonia, and investigated the properties of NETs generated under hypoxia. This study demonstrated that the amount of NETs in pulmonary lesions was greater in patients with pneumonia than in patients without pneumonia and displayed a positive correlation between the amount of NETs and HIF-1α expression. We further demonstrated that the formation of typical lytic NETs was suppressed and round-shaped NETs were generated under hypoxic conditions in vitro. These round NETs were resistant to digestion by the principal NET regulator, DNase I. Focusing on actin rearrangement in neutrophils stimulated under hypoxic conditions, we found that G-actin polymerization and F-actin degradation—both of which are observed time-dependently under normoxic conditions—were disrupted, suggesting that hypoxia mediated the incomplete NET formation. Moreover, neutrophils stimulated under hypoxic conditions possessed cytotoxicity. Accumulation of neutrophils that form degradation-resistant NETs and possess cytotoxicity, which are generated under hypoxic circumstances, are expected to be involved in exacerbation of underlying lung diseases complicated with pneumonia.

scholarly journals Bactericidal/Permeability-Increasing Protein Preeminently Mediates Clearance of Pseudomonas aeruginosa In Vivo via CD18-Dependent Phagocytosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jomkuan Theprungsirikul ◽  
Sladjana Skopelja-Gardner ◽  
Ashley S. Burns ◽  
Rachel M. Wierzbicki ◽  
William F. C. Rigby
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Critical Role ◽  
Chronic Obstructive ◽  
Dependent Manner ◽  
Opsonic Activity ◽  
Obstructive Pulmonary Disease ◽  
Neutrophil Dysfunction ◽  
Chronic Lung Infection

Chronic Pseudomonas aeruginosa infection mysteriously occurs in the airways of patients with cystic fibrosis (CF), bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD) in the absence of neutrophil dysfunction or neutropenia and is strongly associated with autoimmunity to bactericidal permeability-increasing protein (BPI). Here, we define a critical role for BPI in in vivo immunity against P. aeruginosa. Wild type and BPI-deficient (Bpi-/-) mice were infected with P. aeruginosa, and bacterial clearance, cell infiltrates, cytokine production, and in vivo phagocytosis were quantified. Bpi-/- mice exhibited a decreased ability to clear P. aeruginosa in vivo in concert with increased neutrophil counts and cytokine release. Bpi-/- neutrophils displayed decreased phagocytosis that was corrected by exogenous BPI in vitro. Exogenous BPI also enhanced clearance of P. aeruginosa in Bpi-/- mice in vivo by increasing P. aeruginosa uptake by neutrophils in a CD18-dependent manner. These data indicate that BPI plays an essential role in innate immunity against P. aeruginosa through its opsonic activity and suggest that perturbations in BPI levels or function may contribute to chronic lung infection with P. aeruginosa.

scholarly journals Advanced in vitro models of vascular biology: Human induced pluripotent stem cells and organ-on-chip technology

2019 ◽  
Vol 140 ◽  
pp. 68-77 ◽  
Author(s):  
Amy Cochrane ◽  
Hugo J. Albers ◽  
Robert Passier ◽  
Christine L. Mummery ◽  
Albert van den Berg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Vascular Biology ◽  
In Vitro Models ◽  
Chip Technology ◽  
On Chip ◽  
Induced Pluripotent
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