Research

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 […]

A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents

Systemic absorption and metabolism of drugs in the small intestine, metabolism by the liver as well as excretion by the kidney are key determinants of efficacy and safety for therapeutic candidates. However, these systemic responses of applied substances lack in most in vitro assays. In this study, a microphysiological system maintaining the functionality of four organs over 28 […]

ULTRASTRUCTURAL AND HISTOLOGICAL EFFECTS OF EXPOSURE TO CEES OR HEAT IN A HUMAN EPIDERMAL MODEL.

Ultrastructural and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) studies were conducted to compare mechanisms of 2-chloroethyl ethyl sulfide (CEES) and heat-induced injury to EpiDerm™. Twenty-two hours after 2-h exposure to the mono-functional alkylating agent CEES, budding of cytoplasm, clumping of nuclear chromatin, disintegration of nuclear membranes and cytoplasmic structures, and cytoplasmic vacuolization were detected, […]

EPIDERM™ FULL THICKNESS (EPIDERMFT™), A DERMAL/EPIDERMAL SKIN EQUIVALENT WITH A FULLY DEVELOPED BASEMENT MEMBRANE.

Paracrine signaling between dermal fibroblasts and epidermal keratinocytes is believed to modulate skin responses during contact irritant or allergic reactions. Dermal fibroblasats also play an important role in photo-aging and photo-damage, wound healing and cancer progression. To enable in vitro study of these and other dermal phenomena in which fibroblast-epidermal keratinocyte interactions are important, a […]

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 […]

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 […]

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 […]

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 […]

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: […]

EVALUATION OF PRO-INFLAMMATORY BIOMARKERS OF IRRITATION IN HUMAN SKIN MODEL USING MULTIPLEXED IMMUNOASSAY.

EVALUATION OF EPIDERM™ AS A MODEL TO STUDY IRRITATION AFTER EXPOSURE TO VARIOUS ALIPHATIC HYDROCARBONS FOUND IN JET FUELS.

This study by scientists at Florida A&M University College of Pharmacy, Auburn University Harrison School of Pharmacy, and Mattek Corp. demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent is an excellent in vitro alternative to animal testing for evaluating the skin irritation potential of chemicals and jet fuels. JP-8 has been recognized as […]

UVB IRRADIATION OF AN ORGANOTYPIC SKIN MODEL, EPIDERM™, RESULTS IN SIGNIFICANT RELEASE OF CYTOKINES.

Ultraviolet light, especially UVB (290-320 nm), is believed to be responsible for most of the immediate and long term effects of excessive exposure to sunlight. In many cases, the initial stages of these UV induced changes are the release of cytokines. Although cytokine release from human keratinocytes in monolayer cultures following UV exposure has been […]

NEAR-INFRARED OPTICAL SENSORS BASED ON SINGLE-WALLED CARBON NANOTUBES.

This study by researchers in the Chemical/Biomolecular Engineering and Chemistry departments at the University of Illinois demonstrated that Mattek’s EpiDermFT full-thickness in vitro human skin tissue equivalent can be used to mimic in vivo human skin tissues in NIR imaging studies. Molecular detection using near-infrared light between 0.9 and 1.3 eV has important biomedical applications […]

DEVELOPMENT OF A FULL THICKNESS IN VITRO HUMAN SKIN EQUIVALENT (EPIDERM-FT) FOR SULFUR MUSTARD RESEARCH.

This study by scientists at the U.S. Army Medical Research Institute of Chemical Defense and Mattek Corp. demonstrated that Mattek’s EpiDermFT full-thickness in vitro human skin tissue equivalent is an excellent in vitro alternative for studying the effects of human skin exposure to mustard gas. Skin exposure to the chemical warfare agent bis-(â-chloroethyl)sulfide (mustard gas) […]

EFFECTS IN UNIRRADIATED HUMAN TISSUE INDUCED BY RADIATION DAMAGE UP TO 1 MM AWAY.

This study by researchers at Columbia University’s Center for Radiological Research, Finland’s Radiation and Nuclear Safety Authority, and New York City’s Stuyvesant High School demonstrated how Mattek’s EpiDerm in vitro human skin tissue equivalent and EpiDermFT full-thickness in vitro human skin tissue equivalent can be used in vitro to study “bystander effects” of ionizing radiation […]

DETECTING REACTIVE OXYGEN SPECIES IN SKIN USING TWO-PHOTON FLUORESCENCE IMAGING MICROSCOPY.

Reactive oxygen species (ROS) contribute to skin photodamage including photoaging, immunomodulation, actinic keratosis and skin cancers. Because these highly-reactive derivatives of molecular oxygen are extremely short-lived and essentially non-emissive, they are difficult to detect directly. In addition, until recently with the realization of two-photon excited fluorescence (TPEF) imaging, the opaque and heterogeneous environment of the […]

INFLUENCE OF SOYBEAN SYMBIOSOME EXTRACT ON UV-INDUCED SKIN FREE-RADICAL BIOCHEMISTRY.

This study by researchers at Arch Personal Care Products, Arch Chemicals, Bioinnovation Laboratories, Inc., and Dermscan Group demonstrated how Mattek’s EpiDermFT full-thickness in vitro human skin tissue equivalent can be used to measure the ability of a topically-applied formulation to prevent skin damage by inhibiting the expression of nitric oxide free radicals in human (dermal […]

PHOTOPROTECTIVE EFFICACY OF ISOFLAVONE GENISTEIN IN HUMAN RECONSTITUTED SKIN.

This study by researchers in the Mount Sinai School of Medicine Department of Dermatology demonstrated that Mattek’s EpiDermFT full-thickness in vitro human skin tissue equivalent is an excellent in vitro alternative for studying the chemopreventive efficacy of topically applied anti-oxidants relative to UVB radiation exposure. Genistein, the soy plant derived isoflavone, has garnered significant noteworthy […]

HUMAN SKIN EQUIVALENT: A RELIABLE IN VITRO MODEL FOR CARCINOGENIC EXPERIMENTS.

EpiDermFT (Mattek Co., MA) is an in vitro model for human skin derived from keratinocytes of human neonatal foreskin. The epidermal component is cultured to form a highly differentiated model of metabolically and mitotically active cells that are arranged analogous to those found in human epidermal skin. This advanced full-thickness model incorporates a fibroblast-containing dermis […]

RECONSTRUCTED HUMAN SKIN MODEL TO STUDY MELANOMA AT DIFFERENT STAGES OF PROGRESSION.

This study by scientists at Mattek Corp. demonstrated that Mattek’s EpiDerm-FT in vitro human full-thickness skin tissue equivalent can be co-cultured with melanocytes at different stages of malignancy to produce three dimensional, serum-free tissue culture models that can be used to study, understand, and develop preventative and therapeutic treatments for cutaneous melanoma. The incidence of […]

HUMAN MELANOMA DEVELOPMENT IN RECONSTRUCTED SKIN MODELS.

Human skin reconstructs are three dimensional in vitro models consisting of a co-culture of epidermal keratinocytes and melanocytes plated onto a dermal substrate. In contrast to cells in monolayer culture, tissue-engineered skin equivalents contain well-developed epidermal layers with normal melanocytes being distributed at the basement membrane that separates the epidermis from the dermis. The incidence […]

UPREGULATION OF SOX9 INHIBITS THE GROWTH OF HUMAN AND MOUSE MELANOMAS AND RESTORES THEIR SENSITIVITY TO RETINOIC ACID.

This study by researchers at the National Cancer Institute (NIH) demonstrated that Mattek’s Melanoma in vitro human skin tissue equivalent can be used to investigate both the efficacy and cytotoxicity of potential malignant melanoma treatments. Treatments for primary and metastatic melanomas are rarely effective. Even therapeutics such as retinoic acid that are successfully used to […]

A SMALL-MOLECULE E2F INHIBITOR BLOCKS GROWTH IN A MELANOMA CULTURE MODEL.

This study by researchers at the H. Lee Moffitt Cancer Center and Research Institute demonstrated how Mattek’s Melanoma in vitro human skin tissue equivalent can be used to investigate both the efficacy of potential melanoma therapeutic agents and their potential toxicity on non-melanoma skin cells. HLM006474 was identified using a computer-based virtual screen and the […]

HIGHLY DIFFERENTIATED IN VITRO SKIN MODEL FOR HIGH THROUGHPUT SCREENlNG OF TOPICAL THERAPEUTICS.

ROSCOVITINE INHIBITS DIFFERENTIATION AND INVASION IN A THREE-DIMENSIONAL SKIN RECONSTRUCTION MODEL OF METASTATIC MELANOMA.

This study by researchers at the H. Lee Moffitt Cancer Center and Research Institute, and the Mitchell Cancer Institute (Univ. of South Alabama) demonstrated that the Mattek 3-D Melanoma Tissue Model can be used to investigate the therapeutic potential of drugs designed to help patients with metastatic melanoma – in this study, the drug was […]

THE EFFECTS OF TROPOSPHERIC OZONE ON A HUMAN EPIDERMAL SKIN MODEL (EPIDERM).

Recent reports suggest that exposure to tropospheric ozone (O3) poses an oxidative stress to murine skin. So far, no data is available on human skin. Monolayers of human keratinocytes cannot serve as a model of human skin for O3 exposure, since O3 mainly reacts within the stratified stratum corneum (SC). We chose a organotypic model […]

EFFECT OF LAUNDERING ON ABILITY OF GLOVE FABRICS TO DECREASE THE PENETRATION OF ORGANOPHOSPHATE INSECTICIDES THROUGH IN VITRO EPIDERMAL SYSTEMS.

Researchers at Virginia Tech University examined two knit glove fabrics, one of 100% cotton and one of 100% polypropylene, for their capability to decrease the penetration of the organo-phosphate insecticides (OPs), azinphos-methyl and paraoxon after 4 h at field concentrations (3000 and 15 ppm, respectively) through an in vitro epidermal system (Skin2, Advanced Tissue Systems, […]

TOPICALLY APPLIED LACTIC ACID INCREASES SPONTANEOUS SECRETION OF VASCULAR ENDOTHELIAL GROWTH FACTOR/VASCULAR PERMEABILITY FACTOR (VEGF/VPF) BY HUMAN RECONSTRUCTED EPIDERMIS.

Background: Alpha-hydroxy acids (AHAs) are widely used for the treatment of hyperkeratotic skin disorders and photodamaged skin. Objectives: To investigate the effect of lactic acid (LA) on the secretion of cytokines by keratinocytes (KCs) of human reconstructed epidermis. Methods: Creams containing 1.5%, 3% or 5% LA or vehicle controls were topically applied on to human […]

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 […]

TISSUE ABLATION WITH 100-fs AND 200-ps LASER PULSES.

We used water and human skin tissue to compare the surgical potential of 100-fs and 200-ps laser pulses. For investigation of threshold behavior of 100-fs and 200-ps pulses, we use water as a model for tissue. In addition to having a lower threshold, we find that energy deposition is much more consistent with 100-fs pulses. […]

FLAVONOIDS DIFFERENTIALLY REGULATE IFN-GAMMA-INDUCED ICAM-1 EXPRESSION IN HUMAN KERATINOCYTES: MOLECULAR MECHANISMS OF ACTION.

The effect of plant flavonoids on intercellular adhesion molecule-1 (ICAM-1) expression in human keratinocyte was investigated. ICAM-1 is known to mediate skin inflammation. Among the flavonoids tested, taxifolin was the most potent in inhibiting interferon γ (IFN γ)-induced ICAM-1 protein as well as mRNA expression in human keratinocytes. Much smaller dosages of taxifolin were required […]

ALAMAR BLUE DISCLOSES LATENT TOXICITY OF VESICANT IN HUMAN EPIDERMAL MODEL AND CELLS.

A new metabolic activity indicator, alamar blue (AB), was used by researchers at the United States Army Medical Research Institute of Chemical Defense and the State University of New York at Binghamton to estimate cell counts and to observe toxicity in the same human cells at several time points. AB permitted accurate estimates of cell […]

A SYNTHETIC HUMAN EPIDERMAL MODEL CAN DIFFERENTIATE ACUTE FROM LATENT EFFECTS OF THE MONOFUNCTIONAL MUSTARD ANALOGUE, 2-CHLOROETHYLETHYL SULFIDE.

In this study, researchers at the United States Army Medical Research Institute of Chemical Defense and the State University of New York at Binghamton used the metabolic indicator alamar blue (AB) as a noninvasive, fluorescent probe to analyze the toxic effects of the monofunctional sulfur mustard analogue, 2-chloroethylethyl sulfide (CEES). Data from normal human epidermal […]

PHOTOPROTECTIVE EFFECT OF ISOFLAVONE GENISTEIN ON ULTRAVIOLET B-INDUCED PYRIMIDINE DIMER FORMATION AND PCNA EXPRESSION IN HUMAN RECONSTITUTED SKIN AND ITS IMPLICATIONS IN DERMATOLOGY AND PREVENTION OF CUTANEOUS CARCINOGENESIS.

This study by researchers at Mount Sinai School of Medicine demonstrated that Mattek’s EpiDermFT epidermal/dermal human skin tissue equivalent can be used to investigate the photoprotective efficacy of compounds by exposing treated and untreated EpiDermFT tissues to UVB radiation. Genistein, the most abundant isoflavone of the soy derived phytoestrogen compounds, is a potent antioxidant and […]

NOTCH-1 MEDIATED SIGNALING INCREASES IKKα LEVELS – A CRITICAL DETERMINANT CONTROLLING KERATINOCYTE TERMINAL DIFFERENTIATION AND CELL SURVIVAL.

Epidermal formation depends on a balance between cell proliferation, differentiation, and death. While deletion of IKKα gene blocks terminal differentiation in mice, biochemical pathways regulating IKKα in epidermis are unknown. Notch receptors regulate cell fate in response to ligands such as Jagged-1. In normal skin, Jagged-1 is expressed by keratinocytes (KCs) in basal cells and […]

JAGGED-1 MEDIATED ACTIVATION OF NOTCH SIGNALING INDUCES COMPLETE MATURATION OF HUMAN KERATINOCYTES THROUGH NF-B AND PPARγ.

Establishing an effective epidermal barrier requires a series of coordinated molecular events involving keratinocytes (KCs) within a stratified epithelium. Epidermal maturation depends on convergence of pathways involving components of NF-B and peroxisome proliferator activated receptor (PPAR) signaling systems that promote terminal differentiation and production of a stratum corneum. The Notch-1 receptor and its ligand Delta-1 […]

CHARACTERIZATION OF RECONSTRUCTED SKIN MODELS.

The aim of the present study was to evaluate tissue architecture and lipid composition of commercially available reconstructed human skin models; EpiDerm™, SkinEthic™ and Episkin™ in comparison to in-house reconstructed epidermis on a de-epidermized dermis (RE-DED) model and native tissue. For this purpose, the tissue architecture was examined using light microscopy, electron microscopy and immunohistochemistry; […]

EXPRESSION OF CYCLOOXYGENASE IN THE EPIDERM™ HUMAN SKIN MODEL: REGULATION BY ULTRAVIOLET RADIATION AND CYTOKINES.

Cyclooxygenase-2 (COX-2) appears to play an important role in skin carcinogenesis caused by solar ultraviolet radiation (UVR): UVR induces COX-2 expression in human skin, COX-2 activity is upregulated in skin cancers and COX inhibitors reduce UVR-induced tumor formation. In this report, we use RT-PCR, Western blotting and ELISA to study the effect of UVR on […]

ACTIVATION OF NOTCH SIGNALING IN KERATINOCYTES (KC’S) IS NECESSARY AND SUFFICIENT TO CREATE MATURE HUMAN EPIDERMIS.

The signaling system regulating the highly coordinated and programmed series of molecular events that generate a mature, fully differentiated and cornified epidermis is unknown. To determine if Notch ligands and receptors that regulate cell fate decisions in other organ systems may be operative in epidermis, normal human skin was initially examined by immunostaining and Western […]

CROSS-TALK BETWEEN NOTCH SIGNALING AND TWO PATHWAYS REGULATING EPIDERMAL DIFFERENTIATION.

Recently we established that peptides derived from the Notch ligand-Jagged-1 could trigger complete epidermal differentiation using submerged living epidermal equivalents (EEs). Moreover, using a selective inhibitor designed to block Notch receptor activity, epidermal differentiation was also blocked when submerged EEs were raised to an air/liquid interface. To determine the molecular basis by which Notch signaling […]

CHARACTERIZATION OF APOPTOTIC MACHINERY CONTROLLING CELL DEATH IN EPIDERMIS.

Ironically, the functional integrity of epidermis is dependent on a “planned cell death” pathway by which keratinocytes (KCs) undergo terminal differentiation, and then die producing comeocytes. To explore the molecular basis for crucial steps regulating epidermal KC cell death, normal human skin was examined by immunostaining and Western blot analysis. Fractionating KCs by state of […]

HIGHLY DIFFERENTIATED SKIN EQUIVALENT MODEL FOR HIGH THROUGHPUT SCREENING OF TOPICAL THERAPEUTICS.

EpiDerm™ is an in vitro organotypic human skin model cultured at the air/liquid interface to produce a three-dimensional tissue with a stratum corneum possessing a barrier function similar to native epidermis. The model is suitable for topical application of creams or lotions, and has found use in applications including cytotoxicity, irritation, and/or efficacy screening of […]

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 […]

TERMINAL DIFFERENTIATION OF HUMAN KERATINOCYTES AND STRATUM CORNEUM FORMATION IS ASSOCIATED WITH CASPASE-14 ACTIVATION.

Programmed cell death of epidermal keratinocytes (KC) results in the formation of cornified cells, which constitute the outermost skin layer, the stratum corneum. Here we show by reverse transcription-polymerase chain reaction, western blot, and immunohistochemistry that epidermal KC express caspase-14, a member of the caspase family of pro-apoptotic proteases, in a tissue-specific manner. Caspase-14 protein […]

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 […]

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 […]

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 […]

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 […]

GENE EXPRESSION PROFILING OF SKIN CARCINOGENSIS IN MICE.

This study by researchers at the University of Leicester and Unilever’s Safety Environmental Assurance Centre (SEAC) demonstrated that Mattek’s EpiDerm human skin tissue equivalents can be kept in a viable state for up to 23 DAYS. The overall goal of this project, conducted by researchers at the University of Leicester and Unilever’s Safety Environmental Assurance […]

ROLE OF TAURINE ACCUMULATION IN KERATINOCYTE HYDRATION.

Epidermal keratinocytes are exposed to a low water concentration at the stratum corneum stratum granulosum interface. When epithelial tissues are osmotically perturbed, cellular protection and cell volume regulation is mediated by accumulation of organic osmolytes such as taurine. Previous studies reported the presence of taurine in the epidermis of several animal species. Therefore, we analyzed […]

EVIDENCE THAT NITRIC OXIDE IS AN UPSTREAM MEDIATOR OF FASL-MEDIATED KERATINOCYTE APOPTOSIS IN TOXIC EPIDERMAL NECROLYSIS.

Toxic epidermal necrolysis (TEN or Lyell’s syndrome) is a severe adverse drug reaction that results in extensive necrolysis of the skin due to large scale Fas-FasL mediated keratinocyte apoptosis. The signaling pathways leading to the rapid upregulation of keratinocyte FasL expression in TEN are unknown. Here we show that FasL and inducible nitric oxide synthase […]

CHANGES IN CANCER-RELATED GENE EXPRESSION IN AN IN VITRO HUMAN SKIN MODEL FOLLOWING UVB-IRRADIATION.

UV-irradiation causes initiation and promotion of skin cancers, photoaging and immunosuppression. To further our understanding of these processes at the molecular level, we utilized cDNA array technology to examine changes in gene expression in the EpiDerm™ in vitro human skin model following irradiation with UVB (175 ml per cm2). Viability of irradiated EpiDerm tissue, as […]

EFFECTS OF CEES ON INFLAMMATORY MEDIATORS, HEAT SHOCK PROTEIN 70A, HISTOLOGY AND ULTRASTRUCTURE IN TWO SKIN MODELS.

Chemical warfare threats require the development of diverse models for the assessment of countermeasures. Human skin products, Skin2 (differentiating keratinocytes on a fibroblast-collagen matrix) and EpiDerm (differentiating keratinocytes) were exposed (2 h) to the sulfur mustard 2-chloroethyl ethyl sulfide (CEES. 1-2 mg l(-1) min(-1)) in humidified air or to humidified air alone. Tissues were evaluated […]

EXPRESSION OF PLACENTA GROWTH FACTOR CYCLOOXYGENASE AND THYMUS-AND ACTIVATION-REGULATED CHEMOKINE IN THE EPIDERM IN VITRO HUMAN SKIN EQUIVALENT.

In vitro skin equivalent models are finding increased utility as tools in basic skin research, safety assessment and product development processes. To further utilization for these purposes, we are currently defining a growing list of physiologically significant molecular endpoints to monitor the effects of experimental treatments on EpiDerm™ in vitro human skin tissue. In the […]

IL-1-RELATED CYTOKINE RESPONSES OF NONIMMUNE SKIN CELLS SUBJECTED TO CEES EXPOSURE WITH AND WITHOUT POTENTIAL VESICANT ANTAGONISTS.

Sulfur mustard provokes an acute inflammatory response in skin. To determine if keratinocytes regulate this response and whether three potential vesicant antagonists can counteract adverse changes, specimens of EpiDerm™ (Mattek Corp., Ashland, MA), a human skin model of differentiating keratinocytes, were exposed 2 h to humidified air with or without 2-chloroethyl ethyl sulfide (CEES. 1.72-4.73 […]

RECONSTITUTED 3-DIMENSIONAL HUMAN SKIN AS A NOVEL IN VITRO MODEL FOR STUDIES OF CARCINOGENESIS.

EpiDerm (Mattek Co., MA) is a reconstituted human skin equivalent which exhibits morphological and growth characteristics similar to human skin. This model has previously been utilized to evaluate the cytotoxicity and irritant potential of various cosmetic and household products. In this study, we show for the first time that EpiDerm can be used successfully to […]

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 […]

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 […]

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 […]