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Science (New York, N.Y.) Jun 2010Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice...
Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.
Topics: Air; Alveolar Epithelial Cells; Animals; Biomimetic Materials; Blood-Air Barrier; Capillaries; Capillary Permeability; Cells, Cultured; Endothelial Cells; Escherichia coli; Humans; Immunity, Innate; Inflammation; Lung; Mice; Microfluidic Analytical Techniques; Microtechnology; Nanoparticles; Neutrophil Infiltration; Oxidative Stress; Pulmonary Alveoli; Respiration; Silicon Dioxide; Stress, Mechanical
PubMed: 20576885
DOI: 10.1126/science.1188302 -
Cell and Tissue Research Mar 2017The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing... (Review)
Review
The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.
Topics: Animals; Diffusion; Gases; Humans; Lung
PubMed: 27981379
DOI: 10.1007/s00441-016-2541-4 -
Chest Aug 2017Alveolar-pleural fistulas causing persistent air leaks (PALs) are associated with prolonged hospital stays and high morbidity. Prior guidelines recommend surgical repair... (Review)
Review
Alveolar-pleural fistulas causing persistent air leaks (PALs) are associated with prolonged hospital stays and high morbidity. Prior guidelines recommend surgical repair as the gold standard for treatment, albeit it is a solution with limited success. In patients who have recently undergone thoracic surgery or in whom surgery would be contraindicated based on the severity of illness, there has been a lack of treatment options. This review describes a brief history of treatment guidelines for PALs. In the past 20 years, newer and less invasive treatment options have been developed. Aside from supportive care, the literature includes anecdotal successful reports using fibrin sealants, ethanol injection, metal coils, and Watanabe spigots. More recently, larger studies have demonstrated success with chemical pleurodesis, autologous blood patch pleurodesis, and endobronchial valves. This manuscript describes these treatment options in detail, including postprocedural adverse events. Further research, including randomized controlled trials with comparison of these options, are needed, as is long-term follow-up for these interventions.
Topics: Air; Chest Tubes; Chronic Disease; Female; Humans; Lung Diseases; Male; Pleural Diseases; Pleurodesis; Pneumothorax; Practice Guidelines as Topic; Respiratory Tract Fistula; Risk Factors; Sex Factors
PubMed: 28267436
DOI: 10.1016/j.chest.2017.02.020 -
ALTEX 2018The air-blood barrier is mainly composed of alveolar epithelial cells and macrophages. Whereas the epithelium acts as a diffusional barrier, macrophages represent an...
The air-blood barrier is mainly composed of alveolar epithelial cells and macrophages. Whereas the epithelium acts as a diffusional barrier, macrophages represent an immunological barrier, in particular for larger molecules and nanoparticles. This paper describes a new co-culture of human cell lines representing both cell types. Acquiring, culturing and maintaining primary alveolar epithelial cells presents significant logistical and technical difficulties. The recently established human alveolar epithelial lentivirus immortalized cell line, hAELVi, when grown on permeable filters, form monolayers with high functional and morphological resemblance to alveolar type I cells. To model alveolar macrophages, the human cell line THP-1 was seeded on pre-formed hAELVi monolayers. The co-culture was characterized regarding cellular morphology, viability and barrier function. Macrophages were homogenously distributed on the epithelium and could be kept in co-culture for up to 7 days. Transmission electron microscopy showed loose contact between THP-1 and hAELVi cells. When grown at air liquid interface, both cells were covered with extracellular matrix-like structure, which was absent in THP-1 mono culture. In co-culture with macrophages, hAELVi cells displayed similar, sometimes even higher, trans-epithelial electrical resistance than in mono-cultures. When exposed to silver and starch NPs, hAELVi mono-cultures were more tolerant to the particles than THP-1 mono-cultures. The viability in the co-culture was similar to that of hAELVi monocultures. Transport studies with sodium fluorescein in presence/absence of EDTA proved that the co culture acts as functional diffusion barrier. These data demonstrate that hAELVi-/THP-1 co-cultures represent a promising model for safety and permeability studies of inhaled chemicals, drugs and nanoparticles.
Topics: Alveolar Epithelial Cells; Blood-Air Barrier; Cell Line; Coculture Techniques; Humans; Macrophages; Permeability
PubMed: 29169185
DOI: 10.14573/altex.1607191 -
International Journal of Molecular... Apr 2020Gas exchange in the lung takes place via the air-blood barrier in the septal walls of alveoli. The tissue elements that oxygen molecules have to cross are the alveolar... (Review)
Review
Gas exchange in the lung takes place via the air-blood barrier in the septal walls of alveoli. The tissue elements that oxygen molecules have to cross are the alveolar epithelium, the interstitium and the capillary endothelium. The epithelium that lines the alveolar surface is covered by a thin and continuous liquid lining layer. Pulmonary surfactant acts at this air-liquid interface. By virtue of its biophysical and immunomodulatory functions, surfactant keeps alveoli open, dry and clean. What needs to be added to this picture is the glycocalyx of the alveolar epithelium. Here, we briefly review what is known about this glycocalyx and how it can be visualized using electron microscopy. The application of colloidal thorium dioxide as a staining agent reveals differences in the staining pattern between type I and type II alveolar epithelial cells and shows close associations of the glycocalyx with intraalveolar surfactant subtypes such as tubular myelin. These morphological findings indicate that specific spatial interactions between components of the surfactant system and those of the alveolar epithelial glycocalyx exist which may contribute to the maintenance of alveolar homeostasis, in particular to alveolar micromechanics, to the functional integrity of the air-blood barrier, to the regulation of the thickness and viscosity of the alveolar lining layer, and to the defence against inhaled pathogens. Exploring the alveolar epithelial glycocalyx in conjunction with the surfactant system opens novel physiological perspectives of potential clinical relevance for future research.
Topics: Alveolar Epithelial Cells; Animals; Glycocalyx; Humans; Pulmonary Alveoli; Pulmonary Surfactants; Respiratory Mucosa
PubMed: 32349261
DOI: 10.3390/ijms21093075 -
The European Respiratory Journal Jan 2023https://bit.ly/3Tuaffb
https://bit.ly/3Tuaffb
Topics: Humans; COVID-19; Lung; Lung Diseases; Pneumonia
PubMed: 36707227
DOI: 10.1183/13993003.01962-2022