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EpiAirway

1061

Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making

Risk of lung damage from inhaled chemicals or substances has long been assessed using animal models. However, New Approach Methodologies (NAMs) that replace, reduce, and/or refine the use of animals in safety testing such as 2D and 3D cultures are increasingly being used to understand human-relevant toxicity responses and for the assessment of hazard identification. […]
1045

Efficacy and hazards of 425 nm oral cavity light dosing to inactivate SARS-CoV-2

Objective: Using a battery of preclinical tests to support development of a light-based treatment for COVID-19, establish a range of 425 nm light doses that are non-hazardous to the tissues of the oral cavity and assess whether a 425 nm light dose in this non-hazardous range can inactivate SARS-CoV-2 in artificial saliva. Methods: The potential […]
1031

Aichivirus A1 replicates in human intestinal epithelium and bronchial tissue: Lung–gut axis?

The role of aichivirus A1 (AiV-A1) in acute gastroenteritis remains controversial and in vitro data illustrating its pathogenesis in suitable human models are scarce. Here, we demonstrate that AiV-A1 isolate A846/88 replicates in ApoA1- (absorptive) and Ki-67-positive (proliferative) enterocytes in stem cell-derived human small intestinal epithelium (HIE) as well as in patient biopsy samples, but […]
1020

Assessment of Carbon Nanotubes on Barrier Function, Ciliary Beating Frequency and Cytokine Release in In Vitro Models of the Respiratory Tract

The exposure to inhaled carbon nanotubes (CNT) may have adverse effects on workers upon chronic exposure. In order to assess the toxicity of inhaled nanoparticles in a physiologically relevant manner, an air–liquid interface culture of mono and cocultures of respiratory cells and assessment in reconstructed bronchial and alveolar tissues was used. The effect of CNT4003 […]
1012

Evaluation of in vitro rat and human airway epithelial models for acute inhalation toxicity testing

In vivo models (mostly rodents) are currently accepted by regulatory authorities for assessing acute inhalation toxicity. Considerable efforts have been made in recent years to evaluate in vitro human airway epithelial models (HAEM) as replacements for in vivo testing. In the current work, an organotypic in vitro rat airway epithelial model (RAEM), rat EpiAirway, was […]
1009

Multi Species 3D Airway Tissue Models for Translational Inhalation Toxicity Studies

Scalable, reproducible in vitro 3-dimensional organotypic models from different species are needed for translational studies to develop reliable alternatives to traditional in vivo animal inhalation toxicity tests. The aim of this study is to compare toxicity responses of 3D airway tissue models constructed using primary tracheobronchial epithelial cells harvested from rat, primate, and human tissues. […]
1006

Development of a micronucleus test using the EpiAirway™ organotypic human airway model

The use of organotypic human tissue models in genotoxicity has increased as an alternative to animal testing. Genotoxicity is generally examined using a battery of in vitro assays such as Ames and micronucleus (MN) tests that cover gene mutations and structural and numerical chromosome aberrations. At the 7th International Workshop on Genotoxicity Testing, working group […]
1001

Antiviral activity of EIDD-1931 and Remdesivir against SARS-CoV-2 variants in a 3D mucociliary tissue models consisting of normal human-derived tracheal/bronchial (EpiAirway) and nasal (EpiNasal) epithelial cells

In vitro assays are an important early step to determine the potential antiviral activity of novel compounds. The antiviral efficacy of compounds is often evaluated in immortalized cell lines, which offer the advantage of cost effectiveness, ease of use, and reproducibility. However, these monolayer cell lines are not always predictive for cytotoxicity or in vivo […]
1000

Validation of physiologically relevant in vitro human inhalation toxicity tests for volatile liquids, mists, and sprays

In vivo animal models are currently accepted by regulatory authorities for acute respiratory toxicity (ART) testing. However, animal tests have been discredited as predictors of human responses on physiological and ethical grounds. The goal of this work was to develop physiologically relevant ART tests utilizing the EpiAirway™ tissue model, to demonstrate correlation  to  OECD  accepted  […]
991

Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection

The repurposing of licensed drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given circa 7817 licensed compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially available ex vivo/3D airway and alveolar tissue […]
989

Proteomic, Metabolomic, and Lipidomic Analyses of Lung Tissue Exposed to Mustard Gas

Sulfur mustard (HD) poses a serious threat due to its relatively simple production process. Exposure to HD in the short-term causes an inflammatory response, while long-term exposure results in DNA and RNA damage. Respiratory tract tissue models were exposed to relatively low concentrations of HD and collected at 3 and 24 h post exposure. Histology, […]
970

Mitoxantrone modulates a heparan sulfate‑spike complex to inhibit SARS‑CoV‑2 infection

Spike-mediated entry of SARS-CoV-2 into human airway epithelial cells is an attractive therapeutic target for COVID-19. In addition to protein receptors, the SARS-CoV-2 spike (S) protein also interacts with heparan sulfate, a negatively charged glycosaminoglycan (GAG) attached to certain membrane proteins on the cell surface. This interaction facilitates the engagement of spike with a downstream […]
967

Replication and antiviral activity of MERS and SARS-CoV-2 variants in a highly specialized 3D mucociliary tissue model consisting of normal human-derived tracheal/bronchial epithelial cells

In vitro assays are an important early step to determine the potential antiviral activity of novel compounds. The antiviral efficacy of compounds is often evaluated in immortalized cell lines, which offer the advantage of cost effectiveness, ease of use, and reproducibility. However, these monolayer cell lines are not always predictive for cytotoxicity or in vivo […]
954

Petroleum coke exposure leads to altered secretome profiles in human lung models

Petroleum coke (PC) is a coal-like product that is produced during the refinement of crude oil and bituminous sand. Fugitive dust from open storage of PC in urban areas is a potential human health concern. Animal inhalation studies suggest that PC leads to an adverse pulmonary histopathology, including areas of fibrosis and chronic inflammation; however, […]
952

Flagellin From Pseudomonas Aeruginosa Stimulates ATBº,+ Transporter for Arginine and Neutral Amino Acids in Human Airway Epithelial Cells

At present, the central role played by arginine in the modulation of the inflammatory cellular responses is well-recognized, and many pro-inflammatory stimuli are known to modulate the expression and activity of its transmembrane transporters. In this regard, we have addressed the effects of bacterial flagellin from Pseudomonas aeruginosa (FLA-PA) on the uptake of the amino […]
947

In vitro Impact Preliminary Assessment of Airborne Particulate from Metalworking and Woodworking Industries

Inhalation is the main route of exposure to airborne pollutants. To evaluate the safety and assess the risks of occupational hazards different testing approaches are used. 3D airway epithelial tissues allow to mimic exposure conditions in vitro, generates human-relevant toxicology data, allows to elucidate the mode of action of pollutants. Gillian3500 pumps were used to […]
946

Organic Cation Transporters (OCTs/OCTNs) in Human Primary Alveolar Epithelial Cells

Alveolar epithelium, besides exerting a key role in gas exchange and surfactant production, plays important functions in host defense and inflammation. Pathological conditions associated to alveolar dysfunction include Acute Respiratory Distress Syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).The use of predictive in vitro models of human alveolar epithelium is […]
943

Enisamium is an inhibitor of the SARS-CoV-2 RNA polymerase and shows improvement of recovery in COVID-19 patients in an interim analysis of a clinical trial

Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called Coronavirus Disease 2019 (COVID-19). Control of SARS-CoV-2 spread will depend on vaccine-induced or naturally acquired protective herd immunity. Until then, antiviral strategies are needed to manage COVID-19, but approved antiviral treatments, such as remdesivir, can only be delivered intravenously. Enisamium (laboratory code FAV00A, trade name […]
942

AT-527, a Double Prodrug of a Guanosine Nucleotide Analog, Is a Potent Inhibitor of SARS-CoV-2 In Vitro and a Promising Oral Antiviral for Treatment of COVID-19

The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is global and unprecedented. Although remdesivir has recently been approved by the FDA to treat SARS-CoV-2 infection, no oral antiviral is available for outpatient treatment. AT-527, an orally administered double prodrug of a guanosine nucleotide analog, was previously shown to be […]
938

Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant

SARS-CoV-2 Delta variant has rapidly replaced the Alpha variant around the world. The mechanism that drives this global replacement has not been defined. Here we report that Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement. In a replication competition assay, Delta SARS-CoV-2 efficiently outcompeted the Alpha variant in human lung […]
932

Modeling SARS-CoV-2 and Influenza Infections and Antiviral Treatments in Human Lung 2 Epithelial Tissue Equivalents

Sever acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third coronavirus in less than 20 years to spillover from an animal reservoir and cause severe disease in humans. High impact respiratory viruses such a pathogenic beta-coronaviruses and influenza viruses, as well as other emerging respiratory viruses, pose an ongoing global health threat to humans. There is […]
925

Menthol in electronic cigarettes: A contributor to respiratory disease?

Menthol is widely used in tobacco products. This study compared the effects of menthol on human bronchial epithelium using submerged cultures, a VITROCELL® cloud chamber that provides air liquid interface (ALI) exposure without solvents or heating, and a Cultex ALI system that delivers aerosol equivalent to that inhaled during vaping. In submerged culture, menthol significantly […]
924

The N501Y spike substitution enhances SARS-CoV-2 transmission

Beginning in the summer of 2020, a variant of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the United Kingdom (UK). This B.1.1.7 variant increased rapidly in prevalence among sequenced strains, attributed to an increase in infection and/or transmission efficiency. The UK variant has 19 nonsynonymous mutations across its viral genome including 8 substitutions […]
923

Oral Hsp90 inhibitor, SNX-5422, attenuates SARS-CoV-2 replication and dampens 2 inflammation in airway cells.

Currently available SARS-CoV-2 therapeutics are targeted towards moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. While vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for […]
922

A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication

Except remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (Mpro). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 […]
918

The SARS-CoV‑2 Cytopathic Effect Is Blocked by Lysosome Alkalizing Small Molecules

Understanding the SARS-CoV-2 virus’ pathways of infection, virus−host−protein interactions, and mechanisms of virus-induced cytopathic effects will greatly aid in the discovery and design of new therapeutics to treat COVID-19. Chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including alkalizing lysosomes and blocking autophagy as well as exhibiting dose-limiting toxicities […]
913

Influenza A Virus Infection of Human Respiratory Cells Induces Primary MicroRNA Expression*

The cellular response to virus infection is initiated by recognition of the invading pathogen and subsequent changes in gene expression mediated by both transcriptional and translational mechanisms. In addition to well established means of regulating antiviral gene expression, it has been demonstrated that RNA interference (RNAi) can play an important role in antiviral responses. Virus-derived […]
912

A Systems Biology Approach Reveals the Dose- and Time-Dependent Effect of Primary Human Airway Epithelium Tissue Culture After Exposure to Cigarette Smoke In Vitro

To establish a relevant in vitro model for systems toxicology-based mechanistic assessment of environmental stressors such as cigarette smoke (CS), we exposed human organotypic bronchial epithelial tissue cultures at the air liquid interface (ALI) to various CS doses. Previously, we compared in vitro gene expression changes with published human airway epithelia in vivo data to […]
906

Inhibition of Coronavirus Entry In Vitro and Ex Vivo by a Lipid Conjugated Peptide Derived from the SARS-CoV-2 Spike Glycoprotein HRC Domain

The emergence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of the 2019 coronavirus disease (COVID-19), has erupted into a global pandemic that has led to tens of millions of infections and hundreds of thousands of deaths worldwide. The development of therapeutics to treat infection or as prophylactics to halt viral […]
902

Spike mutation D614G alters SARS-CoV-2 fitness and neutralization susceptibility

A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic. However, the mutational impact on viral spread and vaccine efficacy remains to be defined. Here we engineer the D614G mutation in the SARS-CoV-2 USA-WA1/2020 strain and characterize its effect on viral replication, pathogenesis, and antibody neutralization. The D614G mutation significantly enhances SARS-CoV-2 […]
900

Development of an in vitro approach to point-of-contact inhalation toxicity testing of volatile compounds, using organotypic culture and air-liquid interface exposure

In vitro chemical risk assessment using human cells is emerging as an alternative to in vivo animal testing with reduced costs, fewer animal welfare concerns, and the possibility of greater human health relevance. In vitro inhalation toxicity testing of volatile compounds poses particular challenges. Here we report our efforts to establish a testing protocol in […]
899

In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age

Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles of nasopharyngeal (NP) […]
898

PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2

PT150 is a clinical stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; […]
891

Development of a chronic respiratory toxicity assay using an in vitro human airway model

Knowledge of chronic respiratory toxicity potential is important for establishing safe use of chemicals and consumer products. The current work describes efforts to develop an alternative, non-animal method for determining chronic (subacute) respiratory toxicity using the EpiAirway™ in vitro human airway model. Initial acute toxicity experiments were conducted by exposing EpiAirway tissues to four concentrations […]
887

Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently […]
885

In Search of Preventative Strategies: Novel Anti Inflammatory High-CBD Cannabis Sativa Extracts Modulate ACE2 Expression in COVID-19 Gateway Tissues

With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. Similar to other respiratory pathogens, SARS-CoV2 […]
872

Assessment of Biological Responses of EpiAirway™ 3-D Cell Constructs vs. A549 Cells for Determining Toxicity of Ambient Air Pollution

Context — EpiAirway™ 3-D constructs are human-derived cell cultures of differentiated airway epithelial cells that may represent a more biologically relevant model of the human lung. However, limited information is available of its utility for exposures to air pollutants at the air-liquid interface (ALI). Objective — To assess the biological responses of EpiAirway™ cells in […]
871

Dysregulated repair and inflammatory responses by e‐cigarette derived inhaled nicotine and humectant propylene glycol in a sex dependent manner in mouse lung

Nicotine inhalation via electronic cigarettes (e‐cigs) is an emerging concern. However, little is known about the acute toxicity in the lungs following inhalation of nicotine containing e‐cig aerosols. We hypothesized that acute exposure to aerosolized nicotine causes lung toxicity by eliciting inflammatory and dysregulated repair responses. Adult C57BL/6J mice were exposed 2 hours daily for […]
846

An In Vitro Versus In Vivo Toxicogenomic Investigation of Prenatal Exposures to Tobacco Smoke

Approximately 1 million women smoke during pregnancy despite evidence demonstrating serious juvenile and/ or adult diseases being linked to early-life exposure to cigarette smoke. Susceptibility could be determined by factors in previous generations, that is, prenatal or ‘‘maternal’’ exposures to toxins. Prenatal exposure to airborne pollutants such as mainstream cigarette smoke has been shown to […]
843

Toxicological comparison of cigarette smoke and e-cigarette aerosol using a 3D in vitro human respiratory model

With the growing prevalence of e-cigarettes as an alternative to conventional cigarettes amongst smokers worldwide, there is a need for new methods to evaluate their relative toxicological profile as part of a safety assessment. Initiatives to replace, reduce and refine animal testing have led to developments of new methodologies utilizing organotypic, in vitro tissue models. […]
837

Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model

Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal (in vitro) test for determining acute inhalation […]
835

In Vitro Human Airway Models for Study of Goblet Cell Hyperplasia and Mucus Production: Effects of Th2 Cytokines, Double-Stranded RNA, and Tobacco Smoke

Goblet cell hyperplasia (GCH) within the epithelium of the conducting airways is a common feature of human respiratory diseases, including asthma and chronic obstructive pulmonary disease. GCH can be initiated or exacerbated by environmental agents, including air pollution, viral infection, and tobacco smoke. Experimental model systems for investigating causes of GCH and possible remedies are therefore of high […]
817

Mitotic Asynchrony Induces Transforming Growth Factor-b1 Secretion from Airway Epithelium

We recently proposed that mitotic asynchrony in repairing tissue may underlie chronic inflammation and fibrosis, where immune cell infiltration is secondary to proinflammatory cross-talk among asynchronously repairing adjacent tissues. Building on our previous finding that mitotic asynchrony is associated with proinflammatory/fibrotic cytokine secretion (e.g., transforming growth factor [TGF]-b1), here we provide evidence supporting cause-and-effect. Under normal conditions, primary airway epithelial […]
816

Pharmacologically-induced mitotic synchrony in airway epithelial cells as a mechanism of action of anti-inflammatory drugs

Background: Mitotic synchrony is the synchronous progression of a population of cells through the cell cycle and is characteristic of non-diseased airway epithelial cells. However, we previously showed that asthmatic airway epithelial cells are characterized by mitotic asynchrony and are pro-inflammatory as a result. Glucocorticoids can induce mitotic synchrony that in turn suppresses the pro-inflammatory state of diseased […]
794

Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol

Development of physiologically relevant test methods to analyse potential irritant effects to the respiratory tract caused by e-cigarette aerosols is required. This paper reports the method development and optimisation of an acute in vitro MTT cytotoxicity assay using human 3D reconstructed airway tissues and an aerosol exposure system. The EpiAirway™ tissue is a highly differentiated in vitro human […]
806

Antiviral Activity of Ribavirin, 2’,3’-Dideoxicitidine, Pirodavir, Oseltamivir and Infergen™ against RSV, Adeno-2, Rhino-14, Influenza and HCoV-EMC Infection in Differentiated Normal Bronchial Epithelial (dNHBE) Cells

The antiviral activity of ribavirin, 2’,3’-ddC, pirodavir, oseltamivir and Infergen™ was evaluated against respiratory syncytial virus (RSV), adenovirus type 2, rhinovirus type 14, influenza, and human coronavirus HCoV-EMC in a highly differentiated, three-dimensional, ex vivo model of normal human bronchial (dNHBE) cells. Antiviral activity was measured by virus yield reduction assays 3-6 days after infection in the presence of […]
581

ASTHMATIC AIRWAY EPITHELIUM IS INTRINSICALLY INFLAMMATORY AND MITOTICALLY DYSSYNCHRONOUS.

Asthma is an inflammatory condition for which anti-inflammatory glucocorticoids are the standard of care. However, similar efficacy has not been shown for agents targeting inflammatory cells and pathways. This suggests a noninflammatory cell contributor (e.g., epithelium) to asthmatic inflammation. Herein, we sought to define the intrinsic and glucocorticoid-affected properties of asthmatic airway epithelium compared with […]
745

EFFECTS OF GUAIFENESIN, N-ACETYLCYSTEINE, AND AMBROXOL ON MUC5AC AND MUCOCILIARY TRANSPORT IN PRIMARY DIFFERENTIATED HUMAN TRACHEAL-BRONCHIAL CELLS.

Background:  Therapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Several types of drugs are available with different possible modes of action. We examined the effects of guaifenesin (GGE), N-acetylcysteine (NAC) and ambroxol (Amb) on differentiated human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC. Methods:  After IL-13 pre-treatment (3 […]
692

HIGHER LEVEL OF REPLICATION EFFICIENCY OF 2009 (H1N1) PANDEMIC INFLUENZA VIRUS THAN THOSE OF SEASONAL AND AVIAN STRAINS: KINETICS FROM EPITHELIAL CELL CULTURE AND COMPUTATIONAL MODELING.

The pathogenicity and transmission of influenza A viruses are likely determined in part by replication efficiency in human cells, which is the net effect of complex virus-host interactions. H5N1 avian, H1N1 seasonal, and H1N1 2009 pandemic influenza virus strains were compared by infecting human differentiated bronchial epithelial cells in air-liquid interface cultures at relatively low […]
570

TIMECOURSE OF TH2 CYTOKINE-INDUCED GOBLET CELL HYPERPLASIA IN THE EPIAIRWAY™ IN VITRO HUMAN AIRWAY MODEL.

INTRODUCTION: Goblet cell hyperplasia and associated airway re-modeling contribute significantly to the pathogenesis of airway diseases such as asthma, rhinitis and COPD. TH2 cytokines including IL-4 and IL-13 are known to induce goblet cell hyperplasia in various in vivo animal models and in vitro airway cell model systems. However, the timecourse of induction and recovery […]
493

MOLECULAR RESPONSE OF NASAL MUCOSA TO THERAPEUTIC EXPOSURE TO BROAD-BAND ULTRAVIOLET RADIATION.

This study by researchers at MD Anderson Cancer Center (USA), the University of Szeged (Hungary), the Hungarian Academy of Sciences (Hungary), McGill University (Canada) and Victor Babes University (Romania) demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent and EpiDerm in vitro human skin tissue equivalent can be used to model the UV-induced DNA […]
655

IN VITRO EVALUATION OF AIRWAY TOXICITY USING THE EPIAIRWAY ORGANOTYPIC IN VITRO HUMAN AIRWAY MODEL.

Recent REACH legislation has heightened the need for validated in vitro airway toxicity models. However, in vitro determination of airway toxicity potential is problematic since submerged monolayer cell cultures are not amenable to dosing of vapors or water insoluble chemicals. The EpiAirway model is an organotypic air-liquid interface culture produced from normal human airway epithelial […]
566

EVALUATION OF IN VITRO MODELS FOR REACH TOXICITY TESTING: INDUCIBILITY OF XENOBIOTIC METABOLIZING ENZYME (XME) ACTIVITY IN IN VITRO HUMAN AIRWAY (EPIAIRWAY™) AND EPIDERMAL (EPIDERM™) MODELS.

Dermal and airway epithelia contain XMEs including phase I (oxidative) and phase II (conjugative) activities. These XMEs may play a role in biotransformation of drugs and chemicals, leading to altered drug activity or formation of toxic/mutagenic metabolites. Consideration of metabolic activity is therefore important for development of in vitro toxicity/genotoxicty assays required by REACH and […]
572

AN IN VITRO HUMAN AIRWAY MODEL FOR RAPID TOXICITY AND FORMULATION SCREENING OF NASAL DRUG DELIVERY SYSTEMS.

INTRODUCTION: Purpose: Nasal delivery of protein and other high molecular weight drugs is an attractive option to injection or oral delivery. However, nasal drug delivery is limited by potential irritation/toxicity issues, difficulties in achieving effective doses and rapidity of clearance from the nasal cavity. These difficulties are best addressed early in formulation development prior to […]
448

IN VITRO AND IN VIVO SCREENING OF INTRANASAL INSULIN FORMULATIONS.

This study by researchers at Nastech Pharmaceuticals demonstrated that Mattek’s EpiAirway in vitro human tissue equivalents can be used by pharmaceutical companies to develop intranasal drug formulations that provide improved permeation in vivo of Active Pharmaceutical Ingredients (API’s). Nasal delivery of insulin provides an attractive option for a non-invasive diabetes treatment. To identify a suitable […]
654

ORGANOTYPIC IN VITRO HUMAN EPITHELIAL MODELS WITH ENGINEERED TOXICOLOGIC REPORTER FUNCTIONS.

3D organotypic in vitro human epithelial models including skin (e.g. EpiDerm, EpiDerm-FT) and airway (e.g. EpiAirway, EpiAirway-FT) are important advances over traditional monolayer cell culture models. For toxicology applications, these models provide more realistic, in vivo-like structure, barrier properties, metabolic functions and dosing capabilities. In the current poster we describe development of organotypic human epithelial […]
631

FILTER-WELL TECHNOLOGY FOR ADVANCED THREE-DIMENSIONAL CELL CULTURE: PERSPECTIVES FOR RESPIRATORY RESEARCH.

Cell culture has long been a valuable tool for studying cell behaviour. Classical plastic substrates are two-dimensional, and usually promote cellular proliferation and inhibit differentiation. Understanding cell behaviour within complex multicellular tissues requires the systematic study of cells within the context of specific model microenvironments. A model system must mimic, to a certain degree, the […]
481

EXPOSURE OF A MULTI-CELLULAR IN VITRO MODEL OF HUMAN AIRWAY TISSUE TO WHOLE CIGARETTE SMOKE.

This study by researchers at GlaxoSmithKline (GSK) demonstrated that Mattek’s EpiAirwayFT (“full thickness”) human airway in vitro tissue model is a more appropriate physiological model of lung parenchymal tissue than monolayer airway epithelial cell cultures for the analysis of the mechanisms associated with smoking related disease such as inflammation and tissue remodeling and repair. Rationale: […]
740

HUMAN BRONCHIAL EPITHELIAL CELLS EXPOSED IN VITRO TO CIGARETTE SMOKE AT THE AIR-LIQUID INTERFACE RESEMBLE BRONCHIAL EPITHELIUM FROM HUMAN SMOKERS.

Organotypic culture of human primary bronchial epithelial cells is a useful in vitro system to study normal biological processes and lung disease mechanisms, to develop new therapies, and to assess the biological perturbations induced by environmental pollutants. Herein, we investigate whether the perturbations induced by cigarette smoke (CS) and observed in the epithelium of smokers’ […]
642

IN VITRO EXPOSURE OF ORGANOTYPICAL 3D EPITHELIAL TISSUES TO CIGARETTE SMOKE AS A POTENTIAL ALTERNATIVE TO RODENT INHALATION STUDIES.

Airway epithelium is the initial barrier affected by toxic gases or particles in the atmosphere, such as cigarette smoke (CS), which induces, among other things, inflammatory processes that can lead to COPD and tissue remodeling (Takizawa 2001, Yoshida 2007). Here we describe an in vitro test system that examines the toxicological effects of single or […]
562

ESTABLISHMENT OF A 3D AIRWAY MODEL FOR RESPIRATORY INFECTION.

Summary: Battelle utilizes the EpiAirway 3D respiratory tract tissue model for respiratory pathogen infection studies and for comparison of response to infection in the 3D in vitro tissue models derived from normal, asthmatic, smoker, and chronic obstructive pulmonary disease (COPD) donor tissues. Battelle has demonstrated that the EpiAirway tissues can be cultured for extended periods […]
428

CHARACTERISATION OF AIRBORNE PARTICULATE MATTER AND RELATED MECHANISMS OF TOXICITY: AN EXPERIMENTAL APPROACH.

This study by researchers at Cardiff University (UK), the Institute of Earth Sciences Jaume Almera (Spain) and the University of Vermont (USA) demonstrated that Mattek’s EpiAirway human tracheal/bronchial tissue equivalent can be used as an in vitro model to measure the toxicity of nicotine to human respiratory epithelia. For many research laboratories interested in utilizing […]
263

GINGIVAL TISSUE MODEL FOR PREDICTION OF IRRITANCY OF ORAL CARE PRODUCTS.

The development of human reconstructed tissues of the oral cavity that express in vivo-like differentiated characteristics would be important to better understand and develop therapies for gum disease, oral cancer, lesions due to smokeless tobacco, and gingivitis, amongst other diseases of the oral mucosa. In vitro tissue models would be used to assess the biocompatibility […]
494

GENOMIC BIOMARKERS OF PULMONARY EXPOSURE TO TOBACCO SMOKE COMPONENTS.

This study by researchers at the Cardiff University School of Biosciences demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent can be used to accurately model the genetic effects of tobacco smoke component exposure on human respiratory epithelium. Background: Associations between smoking and the development of tobacco-related diseases in humans have historically been assessed […]
483

AN IN VITRO APPROACH TO ASSESS THE TOXICITY OF INHALED TOBACCO SMOKE COMPONENTS: NICOTINE, CADMIUM, FORMALDEHYDE AND URETHANE.

This study by researchers at Cardiff University demonstrated that Mattek’s EpiAirway human airway in vitro tissue model is an excellent tool for screening the toxicity of inhaled compounds. One of the first lines of defence to inhaled toxins is the barrier formed by the tracheobronchial epithelium, making this the ideal region for studying the toxicity […]
482

CELLULAR RESPONSES OF PRIMARY HUMAN BRONCHIAL EPITHELIAL CELLS TO WHOLE CIGARETTE SMOKE EXPOSURE.

This study by researchers at GlaxoSmithKline (GSK) demonstrated that Mattek’s EpiAirway human airway in vitro tissue model combined with the Vitrocell system provided a more physiologically relevant model for studying the effects of cigarette smoke exposure. Rationale: Traditional approaches towards examining the cellular effects of cigarette smoke exposure in vitro have largely relied on the […]
683

UPDATE ON VALIDATION STATUS AND INDUSTRY UTILIZATION OF NORMAL HUMAN 3D (NHU-3D) ANIMAL ALTERNATIVE MODELS.

Progress in in vitro tissue engineering over the last several decades has contributed to a significant decrease in animal use for industrial risk and safety assessment of products and ingredients. Mattek Corporation has a long-standing involvement in development, production and validation of animal alternative in vitro models produced from normal human cells (NHu-3D models). The […]
243

PERMEABILITY AND CYTOTOXICITY OF MACROMOLECULE FROM NASAL FORMULATION USING EPIAIRWAY TISSUE MODEL.

Hydrophilic macromolecules such as proteins and peptides are poorly absorbed through the nasal mucosa. Nastech Pharmaceuticals has utilized a variety of techniques to improve the nasal absorption of macromolecules with emphasize on achieving safety as well as therapeutic efficacy. EpiAirway, an in vitro epithelial cell membrane model, was employed to screen Nastech formulations and marketed […]
442

REGULATORY REQUIREMENTS FOR IN VITRO SYSTEMS TO MEET PERFORMANCE STANDARDS OVER TIME AS WELL AS DURING VALIDATION.

This technical poster by scientists at Mattek Corp. summarized 12-PLUS YEARS (1996-2007) of commercial production QC data for Mattek’s EpiDerm and EpiOcular in vitro human tissue equivalents, and how that data addresses regulatory concerns regarding performance standards of alternative in vitro testing methods over time. In vitro models are being proposed as alternatives to animal […]
707

APPLICATIONS OF THE PHYTOMEDICINE ECHINACEA PURPUREA (PURPLE CONEFLOWER) IN INFECTIOUS DISEASES.

Extracts of Echinacea purpurea (EP, purple coneflower) have been used traditionally in North America for the treatment of various types of infections and wounds, and they have become very popular herbal medicines globally. Recent studies have revealed that certain standardized preparations contain potent and selective antiviral and antimicrobial activities. In addition, they display multiple immune-modulatory […]
704

ADAPTATION OF HUMAN PARAINFLUENZA VIRUS TO AIRWAY EPITHELIUM REVEALS FUSION PROPERTIES REQUIRED FOR GROWTH IN HOST TISSUE.

Paramyxoviruses, a family of RNA enveloped viruses that includes human parainfluenza virus type 3 (HPIV3), cause the majority of childhood croup, bronchiolitis, and pneumonia worldwide. Infection starts with host cell receptor binding and fusion of the viral envelope with the cell membrane at the cell surface. The fusion process requires interaction of the two viral […]
659

USE OF THE EPIAIRWAY MODEL FOR CHARACTERIZING LONG-TERM HOST-PATHOGEN INTERACTIONS.

Nontypeable Haemophilus influenzae (NTHi) are human-adapted Gram-negative bacteria that can cause recurrent and chronic infections of the respiratory mucosa 1; 2. To study the mechanisms by which these organisms survive on and inside respiratory tissues, a model in which successful long-term co-culture of bacteria and human cells can be performed is required. We use primary […]
760

Phenotypic Responses of Differentiated Asthmatic Human Airway Epithelial Cultures to Rhinovirus

Objectives: Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns […]
751

A TRIPLE CELL CO-CULTURE MODEL OF THE AIR-BLOOD BARRIER RECONSTRUCTED FROM PRIMARY HUMAN CELLS.

Reliable in vitro human models for investigating airway toxicity are needed to advance Tox21 efforts to replace animal testing with human-based model systems. In vitro airway models based on primary human cells have been described, however, models based on animal cells or human cell lines are still most commonly employed. In the present work, we […]
755

HUMAN BOCAVIRUS 1 INFECTS COMMERCIALLY AVAILABLE PRIMARY HUMAN AIRWAY EPITHELIUM CULTURES PRODUCTIVELY.

Human bocavirus 1 (HBoV1), a human parvovirus, belongs to the genus Bocavirus of the Parvoviridae family. It causes wheezing in young children with acute respiratory tract infections. HBoV1 has been shown to infect polarized human airway epithelium (HAE) made in house, and induces airway epithelial damage. In this study, two commercially available HAE cultures, EpiAirway […]
753

INTERACTION BETWEEN THE HEMAGGLUTININ-NEURAMINIDASE AND FUSION GLYCOPROTEINS OF HUMAN PARAINFLUENZA VIRUS TYPE III REGULATES VIRAL GROWTH IN VIVO.

Paramyxoviruses, enveloped RNA viruses that include human parainfluenza virus type 3 (HPIV3), cause the majority of childhood viral pneumonia. HPIV3 infection starts when the viral receptor-binding protein engages sialic acid receptors in the lung and the viral envelope fuses with the target cell membrane. Fusion/entry requires interaction between two viral surface glycoproteins: tetrameric hemagglutmin-neuraminidase (HN) […]
752

PREVALENCE AND CHARACTERIZATION OF INFLUENZA VIRUSES IN DIVERSE SPECIES IN LOS LLANOS, COLOMBIA.

While much is known about the prevalence of influenza viruses in North America and Eurasia, their prevalence in birds and mammals in South America is largely unknown. To fill this knowledge gap and provide a baseline for future ecology and epidemiology studies, we conducted 2 years of influenza surveillance in the eastern plains (los Llanos) […]
713

INHIBITION OF HUMAN RESPIRATORY SYNCYTIAL VIRUS INFECTIVITY BY A DENDRIMERIC HEPARAN SULPHATE-BINDING PEPTIDE.

Respiratory syncytial virus (RSV) interacts with cell surface heparan sulphate proteoglycans (HSPGs) to initiate infection. The interaction of RSV with HSPGs thus presents an attractive target for the development of novel inhibitors of RSV infection. In the present study, a minilibrary of linear, dimeric and dendrimeric peptides containing clusters of basic amino acids was screened […]
711

CHARACTERIZATION OF EXTENDED CO-CULTURE OF NON-TYPEABLE HAEMOPHILUS INFLUENZAE WITH PRIMARY HUMAN RESPIRATORY TISSUES.

Non-typeable Haemophilus influenzae (NTHi) are human-adapted Gram-negative bacteria that comprise part of the normal flora of the human upper airway, but are also responsible for a number of mucosal infections such as otitis media and bronchitis. These infections often recur and can become chronic. To characterize the effect of long-term co-culture of NTHi with human […]
414

FORMULATION DEVELOPMENT OF siRNAs FOR DRUG DELIVERY: A NEW THERAPEUTIC APPROACH FOR PANDEMIC INFLUENZA.

This study by scientists at Nastech Pharmaceuticals demonstrated how Mattek’s EpiAirway human tracheal/bronchial tissue equivalent can be used to identify lipids that facilitate siRNA uptake in lung tissue. This was part of a program to develop siRNA-based therapeutics designed for direct-to-lung delivery to treat humans infected with H5N1 Pandemic (Bird) Flu. The risk of an […]
516

HUMAN PARAINFLUENZA VIRUS INFECTION OF THE AIRWAY EPITHELIUM: THE VIRAL HEMAGGLUTININ-NEURAMINIDASE REGULATES FUSION PROTEIN ACTIVATION AND MODULATES INFECTIVITY.

This study by researchers at Weill Medical College of Cornell University, the Australian Animal Health Laboratory/CSIRO, Ohio State University College of Veterinary Medicine and Mount Sinai Hospital demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent provides an ideal system for assessing the interplay of host cell and viral factors in pathogenesis (human parainfluenza […]
503

IL-13 REGULATES CILIA LOSS AND FOXJ1 EXPRESSION IN HUMAN AIRWAY EPITHELIUM.

This study by researchers at UCLA and Washington University School of Medicine demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent is an excellent in vitro model for studying human respiratory diseases that affect ciliated airway cells. Mucociliary clearance is essential to the defense mechanisms of the respiratory system. Loss of normal mucociliary clearance […]
394

LONG TERM CULTURE OF PSEUDOSTRATIFIED TRACHEAL BRONCHIAL EPIAIRWAY™ TISSUES.

This study by scientists at Mattek Corp. demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent remains viable for up to 27 DAYS and can therefore be used in long term studies of chronic respiratory diseases. The highly differentiated EpiAirway tissue model is used to perform inhaled drug delivery, inhalation toxicity, and airway inflammation/irritancy […]
383

MODELLING THE HUMAN BRONCHI AND ITS RESPONSES IN VITRO.

This study by researchers at Unilever’s Safety and Environment Assurance Centre (SEAC) demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent displayed significant morphological and biochemical correlation with both in vitro and in vivo models, re-confirming the potential value of EpiAirway air-liquid interface tissues in modeling the human respiratory tract in vitro. Technological developments […]
758

A CO-CULTURE MODEL OF THE AIR-BLOOD (ALVEOLAR) BARRIER RECONSTRUCTED FROM PRIMARY HUMAN CELLS.

Reliable in vitro human models for investigating airway toxicity are needed to advance Tox21 efforts to replace animal testing with human-based model systems. In vitro airway models based on primary human cells have been described. However, models based on animal cells or human cell lines are still most commonly employed. In the present work, we […]
619

NOTCH SIGNALING PROMOTES AIRWAY MUCOUS METAPLASIA AND INHIBITS ALVEOLAR DEVELOPMENT.

The airways are conduits that transport atmospheric oxygen to the distal alveolus. Normally, airway mucous cells are rare. However, diseases of the airway are often characterized by mucous metaplasia, in which there are dramatic increases in mucous cell numbers. As the Notch pathway is known to regulate cell fate in many contexts, we misexpressed the […]
684

USE OF NORMAL HUMAN 3D (NHU-3D) TISSUE MODELS (EPIDERM™, EPIAIRWAY™) FOR NANOTOXICOLOGY APPLICATIONS

Nanomaterials are increasingly utilized in numerous commercial applications where dermal contact, inhalation, or oral ingestion is likely. However, their toxicological properties are largely unknown. Potential adverse effects of nanoparticle exposure include allergenicity, cytotoxicity, and genotoxicity. Nanomaterials may enter the body by interacting with, and eventually crossing, epithelial barriers including skin, airway, and intestinal epithelium. Once […]
347

THE USE OF FLUORESCENTLY LABELED NANOPARTICLES TO DETERMINE THE EFFECT OF PARTICLE SIZE ON TRANSLOCATION FROM THE LUNG.

Nanoparticles or ultrafine particles, are particles generally considered to be less than 100nm in size. These particles have been implicated in morbidity and other adverse reactions. Due to their small size, these particles may translocate from the lung to remote sites such as the heart, liver, brain or other extrapulmonary organs after inhalation exposure. Additionally, […]
592

IDENTIFICATION OF TIGHT JUNCTION MODULATING LIPIDS.

Tight junctions (TJs) play an important role in regulating paracellular drug transport. The aim of this study was to identify lipids that rapidly and reversibly alter transepithelial electrical resistance (TER) and/or TJ permeability in epithelial tissue. In this study, we developed a screen for identifying lipids that alter TJ properties. Measurement of TER was used […]
456

AN IN VITRO MODEL OF HUMAN AIRWAY EPITHELIUM (EPIAIRWAY) FOR IN VITRO METABOLISM, TOXICITY SCREENING AND DRUG DELIVERY APPLICATIONS.

This study by Mattek Corp. scientists demonstrated that the EpiAirway in vitro human tracheal/bronchial tissue equivalent possesses the in vivo-like physical and biochemical attributes necessary for evaluating the delivery of drugs, metabolism, airway irritation, and toxicity potential of environmental/occupational chemicals. In vitro airway models are urgently needed as alternatives to animal testing for compliance with […]
384

IN VITRO ALTERNATIVES IN INHALATION TOXICOLOGY – WHERE DO WE START?

This study by researchers at Unilever’s Safety and Environment Assurance Centre (SEAC), Novozyme A/S and GlaxoSmithKline demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent is sufficiently in vivo-like to be considered as an in vitro Replacement (one of the 3 R’s) for use in inhalation toxicology studies. The 7th Amendment to EU directive […]
700

CHARACTERIZATION OF DIACETYL VAPOR-INDUCED AIRWAY TOXICITY USING THE HUMAN EPIAIRWAY™ IN VITRO MODEL.

Inhalation exposure to diacetyl vapor in artificial butter flavoring has been associated with the development of bronchiolitis obliterans (BO) in microwave popcorn factory workers. Inhalation of diacetyl vapor has also been shown to cause inflammation and BO-like lung lesions in animal models. EpiAirway tissue was investigated as an in vitro model system to assess the […]
564

ASSAY DEVELOPMENT FOR IN VITRO EVALUATION OF INHALATION TOXICITY USING THE EPIAIRWAY ORGANOTYPIC IN VITRO HUMAN AIRWAY MODEL.

Recent REACH legislation has heightened the need for validated in vitro airway toxicity models. However, in vitro determination of airway toxicity potential is problematic since submerged monolayer cell cultures are not amenable to dosing of vapors or water insoluble chemicals. The EpiAirway model is an organotypic air-liquid interface culture produced from normal human airway epithelial […]
351

A HIGH-THROUGHPUT IN VITRO MODEL OF HUMAN TRACHEAL/ BRONCHIAL EPITHELIUM (EPIAIRWAY™) FOR PRE-CLINICAL SAFETY AND EFFICACY TESTING OF PHARMACEUTICALS.

This study by scientists at Mattek Corp. demonstrated that Mattek’s EpiAirway in vitro 3-D human tracheal/bronchial tissue equivalent can be produced in a 96-well high-throughput microwell plate format in a highly reproducible manner, enabling the use of this format for in vitro irritation/toxicity screening, high content cell and molecular biology assays, as well as drug […]
242

CHARACTERIZATION OF INFLAMMATORY MEDIATOR RELEASE FROM AN IN VITRO HUMAN TRACHEAL/BRONCHIAL EPITHELIAL TISSUE MODEL.

Monolayer cultures of human-derived tracheal/bronchial epithelial (TBE) cells have been instrumental in understanding the mechanisms of respiratory tract pathologies such as cystic fibrosis, asthma, and tracheal and bronchial inflammation. However, cells in monolayer culture lack the differentiated function of normal in vivo tissue. For instance, monolayer cells are not polarized, they lack cilia and tight […]
359

IDENTIFICATION OF INTELLIGENT BIOMARKERS OF EXPOSURE AND HARM IN THE RESPIRATORY EPITHELIAL TO TOBACCO SMOKE COMPONENTS.

This study by researchers in the Cardiff University School of Biosciences (Wales/UK) demonstrated how Mattek’s EpiAirway in vitro human tracheal/ bronchial tissue equivalent can be used to study the early gene response of human respiratory epithelia to tobacco smoke component exposure. A novel toxicological tool, which consists of a differentiated, 3-D, in vitro model of […]
626

A RECOMBINANT SIALIDASE FUSION PROTEIN EFFECTIVELY INHIBITS HUMAN PARAINFLUENZA VIRAL INFECTION IN VITRO AND IN VIVO.

Background: The first step in infection by human parainfluenza viruses (HPIVs) is binding to the surface of respiratory epithelial cells via interaction between viral receptor-binding molecules and sialic acid–containing receptors. DAS181, a recombinant sialidase protein containing the catalytic domain of Actinomyces viscosus sialidase, removes cell surface sialic acid, and we proposed that it would inhibit […]
625

INHIBITION OF NIPAH VIRUS INFECTION IN VIVO: TARGETING AN EARLY STAGE OF PARAMYXOVIRUS FUSION ACTIVATION DURING VIRAL ENTRY.

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a […]
156

RECONSTRUCTED, DIFFERENTIATED AIRWAY EPITHELIAL CULTURES TO MODEL RESPIRATORY INFECTION.

Normal human tracheal-bronchial epithelial cells (NHBE) have been cultured using serum free medium to form a three dimensional tissue-like structure, EpiAirway, that closely resembles the epithelial tissue of the respiratory tract. Histological cross-sections of both the in vitro tissue and a normal human bronchiole reveal a four layer, bipartite structure. Transmission electron microscopy revealed numerous […]
545

COLIPA VALIDATION OF THE RECONSTRUCTED HUMAN SKIN MICRONUCLEUS ASSAY (RSMN): A NOVEL MICRONUCLEUS ASSAY IN A 3D HUMAN SKIN MODEL.

This COLIPA-funded study by scientists at Procter and Gamble, Henkel AG and Co KGaA, L’Oreal, the Institute for In Vitro Sciences (IIVS), Unilever, Beiersdorf AG, KPSS (Kao Professional Salon Services), GlaxoSmithKline (GSK) and Pierre Fabre demonstrated that Mattek’s EpiDerm in vitro 3-D human skin tissue equivalent, when used as the basis for a human skin […]
304

STUDIES OF BYSTANDER EFFECTS IN ARTIFICIAL HUMAN 3D TISSUE SYSTEMS USING A MICROBEAM IRRADIATION.

According to the target theory of radiation-induced effects (1), a central tenet of radiation biology, DNA damage occurs during or very shortly after irradiation of the nuclei in targeted cells, and the potential for biological consequences can be expressed within one or two cell generations. A range of evidence has now emerged that challenges the […]
658

EVALUATION OF XENOBIOTIC METABOLISM IN HUMAN RECONSTRUCTED SKIN MODELS FOR GENOTOXICITY TESTING.

Skin penetration and absorption is a major route of xenobiotic uptake. Skin maintains furthermore capacities to transform chemical substances which was previously shown by transcriptional expression analysis of metabolizing enzymes including CYPs, Flavin-dependent monooxygenases (FMO), N- Acetyltransferases (NAT) and UDP-Glucuronyltransferases (UDP-GT) [1-3]. Their catalytic activity in skin tissue however was rarely specified. Human reconstructed skin […]
445

DNA DOUBLE-STRAND BREAKS FORM IN BYSTANDER CELLS AFTER MICROBEAM IRRADIATION OF THREE-DIMENSIONAL HUMAN TISSUE MODELS.

This study by researchers at the National Cancer Institute (NIH), University of Lethbridge (Canada) and Columbia University demonstrated the ability to use Mattek’s EpiDermFT and EpiAirway in vitro human tissue equivalents as accurate in vitro surrogates to study phenomena known to be deleterious to human health – in this example, the DNA-damaging “bystander effect” of […]
447

SYSTEMATIC IDENTIFICATION OF PROTEASES AND ANTI-PROTEASES IN DEVELOPING PRIMARY AIRWAY EPITHELIAL CELLS BY GLOBAL GENE EXPRESSION.

This study by researchers at Oxford University demonstrated that the genomics of human epithelial tissue development and differentiation can be investigated using standard global gene expression analysis techniques and Mattek’s in vitro human tissue equivalents, in this case EpiAirway in vitro human tissue equivalents, because all Mattek human tissue equivalents are produced from the appropriate […]
644

ASSESSMENT OF AIRWAY GENOTOXICITY POTENTIAL USING THE EPIAIRWAY IN VITRO HUMAN AIRWAY MODEL AND THE COMET ASSAY.

Determination of genotoxic potential is an important consideration for safety assessment of chemicals that may be inhaled following exposure to consumer products, occupational chemicals or environmental pollutants.   Commonly used in vitro genotoxicity assays produce a high rate of false positive results, limiting their practical utility for predicting human genotoxicity hazard.  For assessment  of organ-specific genotoxicity […]
621

GENOTOXICITY TESTING USING THE NORMAL HUMAN CELL BASED 3D EPITHELIAL MODELS.

Safety assessment of new products for human use requires genotoxicity testing to ensure their non-carcinogenicity. Current in vitro genotoxicity assays have low specificity resulting in unacceptably high rates of false positives. Moreover, starting in 2009, in vivo genotoxicity testing was banned by the 7th Amendment to the Cosmetics Directive. Since epithelial tissues have the highest […]
409

DRUG/XENOBIOTIC-METABOLIZING ENZYME (XME) EXPRESSION IN THE EPIAIRWAY IN VITRO HUMAN AIRWAY MODEL: UTILITY FOR ASSESSING TRACHEAL/BRONCHIAL BIOTRANSFORMATION OF INHALED PHARMACEUTICALS AND ENVIRONMENTAL CHEMICALS.

This study by Mattek Corp. scientists demonstrated that Mattek’s EpiAirway human airway tissue equivalent possesses numerous in vivo-like xenobiotic metabolizing enzyme (XME) activities and therefore should be useful for evaluating the airway metabolism of drugs, tobacco smoke and environmental/occupational chemicals. Human tracheal/bronchial epithelium contains xenobiotic metabolizing capabilities provided by a variety of phase I (oxidative) […]
298

REPRODUCIBILITY OF EPIAIRWAY™, A DIFFERENTIATED AIRWAY TISSUE MODEL FOR PRE-CLINICAL DRUG DEVELOPMENT STUDIES.

RATIONALE: Normal human tracheal-bronchial epithelial cells (NHBE) are cultured using serum free medium to form EpiAirway, a three dimensional tissue that closely resembles the epithelial tissue of the respiratory tract. Data was collected by scientists at SUNY Stony Brook and Mattek to determine the lot-to lot reproducibility of EpiAirway and assess its suitability as a […]
344

CANNABIDIOL DIFFUSION ACROSS HUMAN TRACHEO-BRONCHIAL TISSUE (EPIAIRWAY™) AND INTRANASAL ABSORPTION IN RATS.

Some cannabinoids are potentially useful in cancer symptom management to alleviate pain and control chemotherapy-induced nausea and vomiting. The drugs have also been shown to possess anticonvulsant, antianxiety/antipsychotic, and immuno-modulatory effects. The non-psychoactive cannabinoid, cannabidiol (CBD), is a clinical candidate for management of medical conditions where emesis and pain are prevalent. Considering the rapid onset […]
331

PERMEATION OF WIN 55,212-2, A POTENT CANNABINOID RECEPTOR AGONIST, ACROSS HUMAN TRACHEO-BRONCHIAL TISSUE (EPIAIRWAY™) IN VITRO AND RAT NASAL EPITHELIUM IN VIVO.

R-(+)-WIN 55,212-2 is prone to hepatic first-pass metabolism and variable bioavailability following oral administration. The aim of this study was to predict intranasal absorption of the compound using EpiAirway™ tissue culture. Permeation experiments of R-(+)-WIN 55,212-2 mesylate formulations with 2% dimethyl-β-cyclodextrin (DMβCD), 2% randomly methylated-β-cyclodextrin (RAMβCD), 1:1 propylene glycol:saline [PG:S (1:1)] and 1.5% propylene glycol […]
315

DRUG PERMEABILITY ACROSS BOVINE RESPIRATORY TISSUES COMPARED TO A HUMAN TRACHEO/BRONCHIAL CELL CULTURE (EPIAIRWAY™ SYSTEM).

The past three decades have seen the emergence of the nasal mucosa as a viable alternative route for drug delivery. The availability of over 15 drugs meant for systemic action is a testament to its rapidly growing popularity. However, the absence of a good in vitro model precludes the rapid screening of suitable drug compounds […]
314

DOPAMINE TRANSPORT ACROSS RESPIRATORY EPITHELIUM.

Dopamine is a catecholamine neurotransmitter implicated in CNS related disorders such as Parkinson’s disease, schizophrenia and Huntington’s disease. It is known to be transported by the dopamine transporter (DAT) in the CNS and an organic cation transporter (OCT) peripherally. It is orally ineffective due to high first pass metabolism and its inability to cross the […]
310

DEVELOPMENT OF AN INTRANASAL FORMULATION OF THE Y2R AGONIST PEPTIDE YY3-36.

Peptide YY (PYY) was identified in the 1980s as a hormone produced in the gut and as early as 1993 it was demonstrated that peripheral administration of PYY was a satiety factor in mammals and could thus be a potential treatment for obesity. Subsequent research has identified that PYY is released in proportion to the […]
271

AN IN VITRO MODEL FOR THE RAPID SCREENING OF POTENTIAL COMPONENTS AND FORMULATIONS FOR NASAL DRUG DELIVERY.

Clinical trials have indicated that nasal delivery of a variety of drugs is both possible and, in some cases, superior to either injections or oral delivery. The two main drawbacks of nasal delivery are the limited maximum dose per spray and the rapidity of clearance from the nasal cavity. These difficulties can best be addressed […]
244

EFFECTS OF ENHANCERS ON MACROMOLECULES FORMULATIONS ON MEMBRANE PENETRATION, CELL VIABILITY AND RESISTANCE USING EPIAIRWAY™ TISSUE MODEL.

Drug delivery by the nasal route provides many advantages and is an attractive alternative for drugs that cannot be delivered orally and hence typically administered by the parenteral route. Nasal delivery provides an attractive alternative not only because it overcomes the above-mentioned problems with oral delivery, but also due to its fast onset of action, […]
543

RETAINING CELL INTEGRITY DURING ORGANOTYPIC MODEL VIABILITY ASSAYS: ALTERNATIVES TO MTT.

This study by researchers at the State University of New York (SUNY) at Stony Brook documents the effort to the develop an alternative tissue viability endpoint analysis using a non-lytic agent (MTS, Alamar Blue or CalceinAM) in place of the industry-standard MTT for Mattek’s EpiAirway in vitro 3-D human tracheal/bronchial tissue equivalent and Mattek’s EpiDerm […]
542

VALIDATING MTS AS AN ALTERNATIVE VIABILITY ASSAY TO MTT ON THE HUMAN 3-D TISSUE MODELS, EPIAIRWAY AND EPIDERM.

This study by researchers at the State University of New York (SUNY) at Stony Brook documents the development of an alternative tissue viability endpoint analysis using the non-lytic agent MTS in place of the industry-standard MTT for Mattek’s EpiAirway in vitro 3-D human tracheal/bronchial tissue equivalent and Mattek’s EpiDerm in vitro 3-D human skin tissue […]
553

THE EFFICACY OF ECHINACEA IN A 3-D TISSUE MODEL OF HUMAN AIRWAY EPITHELIUM.

This study by researchers at the University of British Columbia and A. Vogel Bioforce AG demonstrated that Mattek’s EpiAirway in vitro 3-D human tracheal/bronchial tissue equivalent can be infected with rhinovirus type 1A (RV1A) and then used to evaluate the antirhinovirus efficacy of Echinacea purpurea. Researchers evaluated the antirhinovirus efficacy of a standardized preparation of […]
552

DAS181, A SIALIDASE FUSION PROTEIN, PROTECTS HUMAN AIRWAY EPITHELIUM AGAINST INFLUENZA VIRUS INFECTION: AN IN VITRO PHARMACODYNAMIC ANALYSIS.

This study by researchers at NexBio and the University of Hong Kong demonstrated that Mattek’s EpiAirway in vitro 3-D human tracheal/bronchial tissue equivalent can be used to model the pharmacodynamics of a new drug formulation that inhibits influenza virus infection. Objectives: The influenza virus (IFV) infection models commonly used to evaluate antiviral agents (e.g. MDCK […]
390

DEVELOPMENT OF A NOVEL HIGH-CONCENTRATION GALANTAMINE FORMULATION SUITABLE FOR INTRANASAL DELIVERY.

This study by researchers at Nastech Pharmaceuticals demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent can be used to assess the drug permeability and cellular toxicity of a novel drug formulation designed for intranasal delivery. The goal of this Nastech Pharmaceutical Co. study was to develop an intranasal formulation of the acetylcholinesterase inhibitor […]
368

INTRANASAL DELIVERY OF RECOMBINANT HUMAN PARATHYROID HORMONE [HPTH (1–34)], TERIPARATIDE IN RATS.

This study by scientists at the University of Kentucky College of Pharmacy and Mattek Corp. demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent can be used to determine the potential toxicity to humans of drugs to be administered intranasally. The aim of this study was to explore the nasal route as an alternative […]
345

LOCALIZATION OF P-GLYCOPROTEIN IN HYMAN TRACHEAL/BRONCHIAL EPITHELIAL CELL CULTURE (EPIAIRWAY™)

The development of a human in vitro cell culture system would enhance the ability to study various factors affecting nasal drug delivery. EpiAirway is a cell culture system derived from normal human tracheal/bronchial epithelial cells which is grown on polycarbonate inserts. It shows a well developed epithelial region and retains the ability to secrete mucus. […]
578

PHARMACOLOGICAL PROPERTIES OF N-(3,5-DIAMINO-6-CHLOROPYRAZINE- 2-CARBONYL)-N’-4-[4-(2,3-DIHYDROXY-PROPOXY)PHENYL]BUTYL-GUANIDINE METHANE-SULFONATE (552-02), A NOVEL EPITHELIAL SODIUM CHANNEL BLOCKER WITH POTENTIAL CLINICAL EFFICACY FOR CYSTIC FIBROSIS.

Amiloride improves mucociliary clearance (MC) by blocking airway epithelial sodium channels (ENaC) and expanding airway surface liquid (ASL). However, the low potency and rapid absorption of amiloride by airway epithelia translated into a short duration of efficacy as an aerosolized therapy for cystic fibrosis (CF) patients. To improve ENaC blocker CF pharmacotherapy, a more potent […]
446

CYTOKINE-INDUCED GOBLET CELL HYPERPLASIA IN THE (EPIAIRWAY-FT) IN VITRO FULL-THICKNESS HUMAN AIRWAY MODEL.

This study by Mattek Corp. scientists demonstrated that Mattek’s EpiAirway-FT in vitro full thickness human airway tissue equivalent is superior to previous airway in vitro tissue equivalents because it provides in vivo-like epithelial cell/fibroblast/matrix interactions, an important aspect of many airway diseases, allowing more accurate in vitro study of these airway phenomena. RATIONALE: In vitro […]
370

MICROARRAY EXPRESSION STUDIES ON AN IN VITRO MODEL OF HUMAN AIRWAY EPITHELIUM (EPIAIRWAY).

This study by researchers at the Wellcome Trust Centre for Human Genetics, Oxford University’s Centre for Gene Function and Mattek Corp. demonstrated how Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent can be used to identify genes and processes involved in the development of human respiratory epithelium and its defenses. Microarray technology now permits analysis […]
521

TISSUE ENGINEERED IN VITRO HUMAN AIRWAY MODELS (EPIAIRWAY) OF ASTHMA AND COPD.

This study by scientists at Mattek Corp. demonstrated that Mattek’s EpiAirway and EpiAirway-FT in vitro human tracheal/bronchial tissue equivalents can be produced from airway epithelium of diseased individuals, and that these tissues are excellent in vitro human models of asthma and COPD providing important unique attributes that animal models cannot provide, including the ability to […]
772

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats

PURPOSE: Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer’s and Parkinson’s diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats. METHODS: Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized […]
508

IN VITRO FORMULATION OPTIMIZATION OF INTRANASAL GALANTAMINE LEADING TO ENHANCED BIOAVAILABILITY AND REDUCED EMETIC RESPONSE IN VIVO.

This study by researchers at Nastech Pharmaceuticals demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent can be used to accurately assess the drug permeability, tight junction modulation, and cellular toxicity of new intranasal drug formulations. The purpose of the current investigation was to optimize an intranasal (IN) galantamine (an acetylcholinesterase inhibitor used for […]
415

PEPTIDES AND PEGYLATED PEPTIDES AS INTRANASAL PERMEATION ENHANCERS: COMPARISON TO SMALL MOLECULAR EXCIPIENTS.

This study by scientists at Nastech Pharmaceuticals demonstrated how Mattek’s EpiAirway human tracheal/bronchial tissue equivalent can be used to identify novel permeation enhancers for use in nasal drug delivery. Intranasal delivery as an alternative route for administering drugs, in particular biologically active peptides, is desirable. Earlier studies by Nastech Pharmaceutical Company scientists showed that a […]
413

THERAPEUTIC UTILITY OF A NOVEL TIGHT JUNCTION MODULATING PEPTIDE FOR ENHANCING INTRANASAL DRUG DELIVERY.

This study by scientists at Nastech Pharmaceuticals demonstrated how Mattek’s EpiAirway human tracheal/bronchial tissue equivalent can be used to test the ability of a novel tight junction modulating (TJM) peptide to enhance the permeability of one low-molecular weight (LMW) drug and three peptides. Previously, a novel tight junction modulating (TJM) peptide was described by Nastech […]
391

PEPTIDE DRUG PERMEATION ENHANCEMENT BY SELECT CLASSES OF LIPIDS.

This study by researchers at Nastech Pharmaceuticals demonstrated that Mattek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent can be used to identify lipids that rapidly and reversibly alter the tight junction permeability of human epithelial tissues. Tight junctions play an important role in regulating paracellular drug transport. The aim of this Nastech Pharmaceutical Co. study […]
774

Airway Epithelial Injury, Fibroblast Changes and Cytokine/Chemokine Profiles Induced by Exposure of Human EpiAirway-FT Tissues to Diacetyl Vapors

Inhalation exposure to diacetyl (DA) vapors in artificial butter flavorings has been associated with the development of obliterative bronchiolitis (OB) in microwave popcorn factory workers. Inhalation of DA vapors has also been shown to cause OB-like lesions in rats. EpiAirway-full thickness (FT) tissue was investigated as an in vitro model to assess the toxicity of […]
765

EARLY HOST RESPONSES OF SEASONAL AND PANDEMIC INFLUENZA A VIRUSES IN PRIMARY WELL-DIFFERENTIATED HUMAN LUNG EPITHELIAL CELLS

Replication, cell tropism and the magnitude of the host’s antiviral immune response each contribute to the resulting pathogenicity of influenza A viruses (IAV) in humans. In contrast to seasonal IAV in human cases, the 2009 H1N1 pandemic IAV (H1N1pdm) shows a greater tropism for infection of the lung similar to H5N1. We hypothesized that host […]
708

CHARACTERIZATION OF THE RETROCYCLIN ANALOGUE RC-101 AS A PREVENTATIVE OF STAPHYLOCOCCUS AUREUS NASAL COLONIZATION.

Nasal colonization of Staphylococcus aureus is a risk factor for pathogenic autoinfection, particularly in postoperative patients and the immunocompromised. As such, standardized preoperative nasal decolonization of S. aureus has become a major consideration for the prevention of nosocomial infection. However, only a few treatment options for nasal decolonization are currently available, with resistance to these […]
641

LTD4 INDUCES HB-EGF-DEPENDENT CXCL8 RELEASE THROUGH EGFR ACTIVATION IN HUMAN BRONCHIAL EPITHELIAL CELLS.

Airway epithelial cells release proinflammatory mediators that may contribute to airway remodeling and leukocyte recruitment. We explored the hypothesis that leukotriene D4 (LTD4) may trigger the release of proremodeling factors through activation of the EGF receptor (EGFR). We particularly focused on the effects of LTD4 on release of heparin-binding EGF-like factor (HB-EGF) and IL-8 (CXCL8), […]
628

SULFUR MUSTARD VAPOR EFFECTS ON DIFFERENTIATED HUMAN LUNG CELLS.

Context:  sulfur mustard (SM) causes skin blistering and long-term pulmonary dysfunction. Its adverse effects have been studied in battlefield-exposed humans, but lack of knowledge regarding confounding factors makes interpretation challenging. Animal studies are critical to understanding mechanisms, but differences between animals and humans must be addressed. Studies of cultured human cells can bridge animal studies […]
617

LIPIDS INCLUDING CHOLESTERYL LINOLEATE AND CHOLESTERYL ARACHIDONATE CONTRIBUTE TO THE INHERENT ANTIBACTERIAL ACTIVITY OF HUMAN NASAL FLUID.

Mucosal surfaces provide first-line defense against microbial invasion through their complex secretions. The antimicrobial activities of proteins in these secretions have been well delineated, but the contributions of lipids to mucosal defense have not been defined. We found that normal human nasal fluid contains all major lipid classes (in micrograms per milliliter), as well as […]
594

EFFECT OF CYCLODEXTRINS ON THE COMPLEXATION AND NASAL PERMEATION OF MELATONIN.

The inclusion complexation of melatonin (MT) with modified cyclodextrins (CDs) was studied with an objective of improving the solubility and nasal absorption of MT. The formation of inclusion complex of MT with Hydroxypropyl âCD (HPâCD) and randomly rnethylated ÂCD (RMâCD) was characterized in solution and solid states by phase solubility and differential scanning calorimetry analyses. […]
484

CD137/CD137L EXPRESSION AND SIGNALING IN IN VITRO MODELS OF HUMAN AIRWAY EPITHELIUM, DENDRITIC CELLS AND T-CELLS.

This study by scientists at Mattek Corp. demonstrated that Mattek’s EpiAirway in vitro human airway tissue model and Mattek’s Human Dendritic Cells are excellent in vitro models for studying the signaling of CD137, a potent T-cell co-stimulatory molecule related to human diseases including cancer and asthma. CD137 is a potent T-cell co-stimulatory molecule that has […]
509

ROLE OF TOLL-LIKE RECEPTOR (TLR) ACTIVATION IN ASTHMA EXACERBATION: EXPERIMENTS WITH IN VITRO MODELS OF HUMAN AIRWAY EPITHELIAL CELLS (EPIAIRWAY) AND EPITHELIAL CELL/FIBROBLAST CO-CULTURES (EPIAIRWAY-FT).

This study by Mattek Corp. scientists demonstrated that Mattek’s EpiAirway and EpiAirway-FT in vitro human tracheal/bronchial tissue equivalents are excellent tools for performing mechanistic studies of signaling pathways related to asthma exacerbations. INTRODUCTION: Respiratory infections are a major cause of asthma exacerbations. The airway epithelium expresses innate responses to infectious agents via TLRs. We investigated […]
168

RECONSTRUCTED, DIFFERENTIATED AIRWAY EPITHELIAL CULTURES TO DETECT OCCUPATIONAL ASTHMA CAUSING AGENTS.

Normal human tracheal-bronchial epithelial cells (NHBE) have been cultured using serum free medium to form a three dimensional tissue-like structure that closely resembles the epithelial tissue of the respiratory tract. Histological cross-sections of both the in vitro tissue and a normal human bronchiole reveal a four layer, bipartite structure. Transmission electron microscopy revealed numerous cilia […]
696

HISTAMINE MAY INDUCE AIRWAY REMODELING THROUGH RELEASE OF EPIDERMAL GROWTH FACTOR RECEPTOR LIGANDS FROM BRONCHIAL EPITHELIAL CELLS

Asthma is a chronic inflammatory disease that is associated with airway remodeling, including hyperplasia of airway epithelial cells and airway smooth muscle cells, and goblet cell differentiation. We wished to address the potential role of histamine, a key biogenic amine involved in allergic reactions, in airway remodeling through the epidermal growth factor receptor (EGFR) pathway. […]
332

AN IN VITRO MODEL OF FULL-THICKNESS HUMAN AIRWAY EPITHELIUM (EPIAIRWAY-FT) FOR STUDY OF EPITHELIUM/MATRIX INTERACTIONS.

In vitro models of airway epithelium (AE) have potential utility for study of diseases such as asthma and COPD, development of inhalable therapeutics, and toxicology of hazardous chemicals. However, degradation and remodeling of subepithelial stromal tissue are important aspects of many airway disease states, and are strongly influenced by fibroblasts (FB) residing in stromal tissue. […]
731

APPLICATION OF ORGANOTYPIC IN VITRO HUMAN CELL CULTURE MODELS FOR RESEARCH AND DEVELOPMENT OF INHALATION PHARMACEUTICAL FORMULATIONS TARGETING THE PROXIMAL AIRWAYS.

Delivery of pharmaceuticals via inhalation is a potentially useful alternative to intravenous injection for drugs that are unstable or poorly absorbed after oral administration; for chronic disease conditions that require frequent administration: or therapeutics for which the airways are the intended target. The proximal airways are common targets for drugs Intended to treat inflammatory conditions […]
591

CIGARETTE SMOKE ALTERS TISSUE INHIBITOR OF METALLOPROTEINASE 1 AND MATRIX METALLOPROTEINASE 9 LEVELS IN THE BASOLATERAL SECRETIONS OF HUMAN ASTHMATIC BRONCHIAL EPITHELIUM IN VITRO.

Background: Asthma, a major cause of chronic lung disease worldwide, has increased in prevalence in all age and ethnic groups, particularly in urban areas where cigarette smoking is common. Cigarette smoke (CS) significantly impacts the development of asthma and is strongly associated with increased asthma-related morbidity. Purpose: To evaluate bioinformatic analyses predicting that CS would […]
410

TH2 CYTOKINE STIMULATED AIRWAY EPITHELIAL CELLS DEMONSTRATE GRANULE-DEPENDENT FasL LOCALIZATION.

This study by researchers at St. Paul’s Hospital / University of British Columbia demonstrated how Mattek’s EpiAirway human airway tissue equivalent can be used to investigate if the localization and presentation of an airway epithelial cell constituent, Fas Ligand (FasL), is dependant on the inflammatory state of the airway tissue. Background: Airway epithelium has been […]
267

TUMOR NECROSIS FACTOR ALPHA (TNFα) INDUCTION OF THYMUS AND ACTIVATION REGULATED CHEMOKINE (TARC) EXPRESSION IS MEDIATED BY 15-LIPOXYGENASE 15-(LOX)-2 IN THE EPIAIRWAY™ HUMAN TRACHEAL/BRONCHIAL EPITHELIAL MODEL.

RATIONALE: T-Helper 2-type (TH2) T cells play a predominant role in human airway inflammation and asthma. TARC, a specific chemoattractant for TH2 cells, is induced by TNFα treatment of human airway cells, however, the cellular pathways involved in mediating TARC induction by TNFα are not fully understood. METHODS: Researchers at the Vanderbilt University School of […]
256

EXPRESSION OF 15-LIPOXYGENASE-2 IN THE EPIAIRWAY™ IN VITRO HUMAN TRACHEAL/BRONCHIAL EPITHELIAL MODEL: REGULATION BY TNF-α AND INF-γ.

15-Hydroxyeicosatetraenoic acid (15[S]-HETE) is the predominate arachidonic acid (AA) metabolite produced by human tracheal/bronchial tissue. This product of the 15-lipoxygenase (15-LOX) enzyme is believed to play a significant role in human airway inflammation and respiratory diseases including cystic fibrosis and asthma. In the current work performed by scientists at Vanderbilt University School of Medicine and […]
495

RECONSTRUCTED EPIDERMIS AND FULL-THICKNESS SKIN FOR ABSORPTION TESTING: INFLUENCE OF THE VEHICLES USED ON STEROID PERMEATION.

This study by researchers at the Free University of Berlin demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent and EpiDermFT full-thickness in vitro human skin tissue equivalent can be used in the development of topical dermatics and for hazard analysis of toxic compounds and their formulations. A protocol for percutaneous absorption studies has […]
782

Predicting Respiratory Toxicity Using a Human 3D Airway (EpiAirway™) Model Combined with Multiple Parametric Analysis

The objective of this study was to assess the potential for an in vitro three-dimensional human airway model (Epi-AirwayTM) to accurately predict respiratory toxicity in humans. This was done by exposing EpiAirway tissues to known respiratory toxicants and assessing tissue viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [MTT] assay and histology), oxidative stress of the tissues (cellular glutathione [GSH] […]