Understanding and manipulating morphogenetic processes to generate in vitro models of airways.

Branching morphogenesis, the process by which cells and tissues organize into complex branched tubular structures, is fundamental to the development of functional organs, including the respiratory airways in mammalian lungs. Advances in understanding the molecular and cellular mechanisms driving morphogenetic processes have enabled the development of sophisticated in vitro models that mimic the structure and function of airways. This review recapitulates developmental principles guiding airway morphogenesis, including the key signaling pathways, cellular interactions, and the different biochemical and mechanical cues.

CXCR4 Blockade Alleviates Pulmonary and Cardiac Outcomes in Early COPD.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease lacking effective treatment. Focusing on early COPD should help to discover disease modifying therapies. We examined the role of the CXCL12/CXCR4 axis in early COPD using human samples and murine models.

A novel tubular model to recapitulate features of distal airways: the bronchioid.

Background: Airflow limitation is the hallmark of obstructive pulmonary diseases, with the distal airways representing a major site of obstruction. Although numerous models of bronchi already exist, there is currently no culture system for obstructive diseases that reproduces the architecture and function of small airways. Here, we aimed to engineer a model of distal airways to overcome the limitations of current culture systems.

Innovative three-dimensional models for understanding mechanisms underlying lung diseases: powerful tools for translational research.

Chronic lung diseases result from alteration and/or destruction of lung tissue, inevitably causing decreased breathing capacity and quality of life for patients. While animal models have paved the way for our understanding of pathobiology and the development of therapeutic strategies for disease management, their translational capacity is limited. There is, therefore, a well-recognised need for innovative models to reflect chronic lung diseases, which will facilitate mechanism investigation and the advancement of new treatment strategies.

Short-range interactions between fibrocytes and CD8 T cells in COPD bronchial inflammatory response.

Bronchi of chronic obstructive pulmonary disease (COPD) are the site of extensive cell infiltration, allowing persistent contact between resident cells and immune cells. Tissue fibrocytes interaction with CD8 T cells and its consequences were investigated using a combination of , experiments and mathematical modeling. We show that fibrocytes and CD8 T cells are found in the vicinity of distal airways and that potential interactions are more frequent in tissues from COPD patients compared to those of control subjects.

Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting.

Chronic obstructive pulmonary disease (COPD) is a worldwide prevalent respiratory disease mainly caused by tobacco smoke exposure. COPD is now considered as a systemic disease with several comorbidities. Among them, skeletal muscle dysfunction affects around 20% of COPD patients and is associated with higher morbidity and mortality.

Probabilistic cellular automata modelling of intercellular interactions in airways: complex pattern formation in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent lung disease characterized by chronic inflammation and tissue remodeling possibly induced by unusual interactions between fibrocytes and CD8+ T lymphocytes in the peribronchial area. To investigate this phenomenon, we developed a probabilistic cellular automata type model where the two types of cells follow simple local interaction rules taking into account cell death, proliferation, migration and infiltration. We conducted a rigorous mathematical analysis using multiscale experimental data obtained in control and disease conditions to estimate the model's parameters accurately.

Cellular interplay in skeletal muscle regeneration and wasting: insights from animal models.

Skeletal muscle wasting, whether related to physiological ageing, muscle disuse or to an underlying chronic disease, is a key determinant to quality of life and mortality. However, cellular basis responsible for increased catabolism in myocytes often remains unclear. Although myocytes represent the vast majority of skeletal muscle cellular population, they are surrounded by numerous cells with various functions.

Muscarinic receptor M3 activation promotes fibrocytes contraction.

Fibrocytes are monocyte-derived cells able to differentiate into myofibroblasts-like cells. We have previously shown that they are increased in the bronchi of Chronic Obstructive Pulmonary Disease (COPD) patients and associated to worse lung function. COPD is characterized by irreversible airflow obstruction, partly due to an increased cholinergic environment.

Asthmatic bronchial smooth muscle increases rhinovirus replication within the bronchial epithelium.

Rhinovirus (RV) infection of the bronchial epithelium is implicated in the vast majority of severe asthma exacerbations. Interestingly, the susceptibility of bronchial epithelium to RV infection is increased in persons with asthma. Bronchial smooth muscle (BSM) remodeling is an important feature of severe asthma pathophysiology, and its reduction using bronchial thermoplasty has been associated with a significant decrease in the exacerbation rate.

Rhinovirus infection of bronchial epithelium induces specific bronchial smooth muscle cell migration of severe asthmatic patients.

Background: Patients with severe asthma show an increase in both exacerbation frequency and bronchial smooth muscle (BSM) mass. Rhinovirus (RV) infection of the bronchial epithelium (BE) is the main trigger of asthma exacerbations. Histological analysis of biopsies shows that a close connection between BE and hypertrophic BSM is a criterion for severity of asthma.

Determination of reliable lung function parameters in intubated mice.

Background: Animal models and, in particular, mice models, are important tools to investigate the pathogenesis of respiratory diseases and to test potential new therapeutic drugs. Lung function measurement is a key step in such investigation. In mice, it is usually performed using forced oscillation technique (FOT), negative pressure-driven forced expiratory (NPFE) and pressure-volume (PV) curve maneuvers.

Fibrocyte accumulation in the airway walls of COPD patients.

The remodelling mechanism and cellular players causing persistent airflow limitation in COPD remain largely elusive. We have recently demonstrated that circulating fibrocytes, a rare population of fibroblast-like cells produced by the bone marrow stroma, are increased in COPD patients during an exacerbation. We aimed to quantify fibrocyte density in bronchial specimens from both control subjects and COPD patients, to define associations with relevant clinical, functional and computed tomography (CT) parameters, and to investigate the effect of the epithelial microenvironment on fibrocyte survival ("Fibrochir" study).

Chemokines in COPD: From Implication to Therapeutic Use.

Chronic Obstructive Pulmonary Disease (COPD) represents the 3rd leading cause of death in the world. The underlying pathophysiological mechanisms have been the focus of extensive research in the past. The lung has a complex architecture, where structural cells interact continuously with immune cells that infiltrate into the pulmonary tissue.

Fibrocytes in Asthma and Chronic Obstructive Pulmonary Disease: Variations on the Same Theme.

Fibrocytes are circulating cells that have fibroblast properties. They are produced by the bone marrow stroma, and they move from the blood to injured organs using multiple chemokine pathways. They exhibit marked functional and phenotypic plasticity in response to the local tissue microenvironment to ensure a proinflammatory or a more resolving phenotype.

Selective dysfunction of p53 for mitochondrial biogenesis induces cellular proliferation in bronchial smooth muscle from asthmatic patients.

Background: Increase of bronchial smooth muscle (BSM) mass is a crucial feature of asthma remodeling. The mechanisms of such an increased BSM mass are complex but involve enhanced mitochondrial biogenesis, leading to increased proliferation of BSM cells in asthmatic patients. The major tumor suppressor protein p53 is a key cell regulator involved in cell proliferation and has also been implicated in mitochondrial biogenesis.

Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial fibrosis. The chronic course of COPD is worsened by recurrent acute exacerbations.

Objective: The aim of the study was to evaluate the recruitment of blood fibrocytes in patients with COPD during exacerbations and, subsequently, to identify potential mechanisms implicated in such recruitment.

Bronchial Smooth Muscle Remodeling in Nonsevere Asthma.

Rationale: Increased bronchial smooth muscle (BSM) mass is a key feature of airway remodeling that classically distinguishes severe from nonsevere asthma. Proliferation of BSM cells involves a specific mitochondria-dependent pathway in individuals with severe asthma. However, BSM remodeling and mitochondrial biogenesis have not been examined in nonsevere asthma.

Subrepellent doses of Slit1 promote Netrin-1 chemotactic responses in subsets of axons.

Background: Axon pathfinding is controlled by guidance cues that elicit specific attractive or repulsive responses in growth cones. It has now become clear that some cues such as Netrin-1 can trigger either attraction or repulsion in a context-dependent manner. In particular, it was recently found that the repellent Slit1 enables the attractive response of rostral thalamic axons to Netrin-1.

Adhesive micropatterns to study intermediate filament function in nuclear positioning.

The nucleus is generally found near the cell center; however its position can vary in response to extracellular or intracellular signals, leading to a polarized intracellular organization. Nuclear movement is mediated by the cytoskeleton and its associated motors. While the role of actin and microtubule cytoskeletons in nuclear positioning has been assessed in various systems, the contribution of intermediate filaments is less established due in part to the lack of tools to study intermediate filament functions.

Calcium channel blocker reduces airway remodeling in severe asthma. A proof-of-concept study.

Rationale: Severe asthma is a major public health issue throughout the world. Increased bronchial smooth muscle (BSM) mass, a characteristic feature of airway remodeling in severe asthma, is associated with resistance to high-intensity treatment and poor prognosis. In vitro, the Ca(2+)-channel blocker gallopamil decreased the proliferation of BSM cells from patients with severe asthma.