Immunological Research

Use of In Vitro Human Skin Models to Assess Potential Immune Activation In Response to Biotherapeutic Attributes and Process-related Impurities

Subcutaneous (SubQ) injection is a common administration route for biotherapeutics. However, limited tools are available for understanding the dynamic relationships between drug products and resident cells following injection. Advances in tissue engineering have enabled the production of in vitro skin models that recapitulate the morphological structure and functional activity of human skin. Here we explore […]

Endo-glucanase digestion of oat β-Glucan enhances Dectin-1 activation in human dendritic cells

Oat β-Glucans were studied for their immunological impact before and after enzymatic digestion in order to enhance the efficacy of oat β-Glucans for application in functional foods. Oat β-Glucan is reported to have minimal impact compared to its fungal counterpart in vitro. Digestion with endo-glucanase enhanced its efficacy towards stimulating MCP-1, RANTES, IL-8, and IL-4 production in human dendritic […]

THE RETROCYCLIN ANALOGUE RC-101 PREVENTS HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INFECTION OF A MODEL HUMAN CERVICOVAGINAL TISSUE CONSTRUCT.

This study by researchers at the University of Central Florida, University of Pittsburgh and UCLA School of Medicine demonstrated that Mattek’s EpiVaginal human vaginal-ectocervical tissue equivalent can be used to test the toxicity and efficacy of potential HIV-1 topical microbicides. Retrocyclins are cyclic antimicrobial peptides that exhibit potent activity towards a broad range of primary […]

RECONSTRUCTED HUMAN VAGINAL-ECTOCERVICAL TISSUE MODELS.

Acquired immunodeficiency syndrome (AIDS) is now the fourth most common cause of death worldwide. In the last 20 years, more than 60 million people have been infected with the virus. By the end of 2002, an estimated 42 million people globally were living with HIV and the majority of new infections occurred in young adult […]

DIFFERENTIAL REGULATION OF â-DEFENSIN EXPRESSION IN HUMAN SKIN BY MICROBIAL STIMULI.

This study by researchers at UCLA’s David Geffen School of Medicine and Lund University (Sweden) demonstrated that Mattek’s EpiDerm in vitro human skin tissue equivalent can be used to study the pathways that connect infection and inflammation with the induction of antimicrobial peptides in epithelia. In response to infection, epithelia mount an innate immune response […]

INJURY ENHANCES TLR2 FUNCTION AND ANTIMICROBIAL PEPTIDE EXPRESSION THROUGH A VITAMIN D–DEPENDENT MECHANISM.

This study by researchers at UCSD, UCLA, UCSF, the University of Michigan and Schering AG demonstrated that Mattek’s EpiDerm human skin tissue equivalent can be used to study the effects of vitamin D3 on the human epidermis, specifically on keratinocytes, enabling them to recognize and respond to microbes, and to protect wounds against infection. An […]

INJURY-INDUCED INNATE IMMUNE RESPONSE IN HUMAN SKIN MEDIATED BY TRANSACTIVATION OF THE EPIDERMAL GROWTH FACTOR RECEPTOR.

This study by researchers at the UCLA School of Medicine (USA) and Lund University (Sweden) demonstrated that sterile wounding of Mattek’s EpiDerm human skin tissue equivalent initiates an in vivo-like innate immune response that increases resistance to overt infection and microbial colonization. Researchers found that sterile wounding of human skin induced epidermal expression of the […]

DEVELOPMENT OF A HUMAN ORAL EPITHELIAL TISSUE MODEL TO STUDY HIV TRANSMISSION AND THE ROLE OF BETA-DEFENSINS.

This study by scientists at the University of Washington and Mattek Corp. demonstrated that Mattek’s EpiOral in vitro human buccal (inner cheek) tissue equivalent can be used for studying the effect of beta-defensins (hBD) on oral HIV transmission. Background: As part of innate immunity, oral mucosal epithelial cells secrete a class of antimicrobial peptides termed […]

THE USE OF PLASMACYTOID DENDRITIC CELLS FOR ALLERGENICITY SCREENING OF CHEMICALS.

This study by Mattek Corp. scientists demonstrated that increased expression of CD86 in pDC’s, a subset of Mattek’s Human Dendritic Cells, can be used as a sensitive and specific marker for the identification of chemical allergens. Also see TR-449 – it contains more recent pDC allergenicity information. Development of a predictive test system to screen […]

IN HUMAN EPIDERMIS, BETA-DEFENSIN 2 IS PACKAGED IN LAMELLAR BODIES.

The skin presents a mechanical, as well as an immunological barrier to infection, and displays considerable innate immune capacity. Recently, cultured human keratinocytes were described to produce and export a microbicidal peptide human-defensin 2 (HBD-2). Immunogold was used to label ultrathin cryosections of stimulated, cultured human epidermis. HBD-2 was found to be stored in the […]

HUMAN β-DEFENSIN EXPRESSION IN A NEW BUCCAL EPITHELIAL TISSUE MODEL.

Oral epithelia function as microbial barriers against bacteria and yeast that are resident in the oral cavity. These microbes can be categorized as non-pathogenic (commensal) and pathogenic (resulting in cavities, gingivitis, and periodontal disease, etc.). The epithelium is actively involved in recognition and response to bacteria, setting into motion the innate immune responses that are […]

GENETICALLY-ENGINEERED IL-10-SECRETING KERATINOCYTES CONDITION LANGERHANS CELLS TOWARDS A TOLERAGENIC PHENOTYPE.

This study by researchers at the State University of New York at Stony Brook demonstrated that Mattek’s Human Dendritic (Langerhans) Cells can be used to determine the influence of epithelial cells and cytokines on Langerhans cell activation and phenotype in response to microbial challenge. Epidermal Langerhans cells (Mattek Corp.), “sentinels” of the epithelium, undergo increased […]

EXPRESSION OF BETA-DEFENSINS IN RESPONSE TO HIV-1 IN AN ORAL TISSUE MODEL VS MONOLAYER CULTURES.

This study by researchers at the University of Washington and the Fred Hutchinson Cancer Research Center demonstrated that Mattek’s EpiOral in vitro human buccal (inner cheek) tissue equivalent can be used to investigate the expression of human beta-defensins (hBD) in response to exposure to HIV-1 virus. HIV transmission through the oral route is inefficient. Epithelial […]

IRRITATION TESTING OF CONTRACEPTIVE AND FEMININE-CARE PRODUCTS USING EPIVAGINAL, AN IN VITRO HUMAN VAGINAL-ECTOCERVICAL TISSUE MODEL.

ORGANOTYPIC ECTOCERVICO-VAGINAL TISSUE MODEL CONTAINING DENDRITIC CELLS.

Acquired immunodeficiency syndrome (AIDS) is now the fourth most common cause of death worldwide. In the last 20 years, more than 60 million people have been infected with the virus. By the end of 2001, an estimated 40 million people globally were living with HIV, and the majority of new infections occurred in young adult […]

ORGANOTYPIC HUMAN ORAL TISSUE MODELS FOR TOXICOLOGICAL STUDIES.

This study by researchers at Procter & Gamble Co., the University of Iowa and Mattek Corp. demonstrated that Mattek’s EpiOral and EpiGingival human oral cavity tissue equivalents can be used to screen the irritation potential of newly developed oral care products and will be useful to study the innate immunity, biology and pathology of the […]

ACTIVATED CD34-DERIVED LANGERHANS CELLS MEDIATE TRANSINFECTION WITH HUMAN IMMUNODEFICIENCY VIRUS.

This study by researchers at Northwestern University’s Feinberg School of Medicine and the University of Illinois at Chicago College of Medicine demonstrated that it was possible to create and isolate a Langerhans Cells (LCs) subset of Mattek Human Dendritic Cells (DC-100) that exhibited the morphological, ultrastructural and cell surface markers exhibited by Langerhans Cells in […]

IN VITRO DERIVED DENDRITIC CELLS TRANS-INFECT CD4 T CELLS PRIMARILY WITH SURFACE-BOUND HIV-1 VIRIONS.

This study by researchers at the University of California at San Francisco (UCSF) demonstrated that Mattek’s Human Dendritic Cells can be used to study the infection mechanism of HIV-1 virus from dendritic cells to T cells. In the prevailing model of HIV-1 trans-infection, dendritic cells (DCs) capture and internalize intact virions and transfer these virions […]

LANGERHANS CELLS RELEASE PROSTAGLANDIN D2 IN RESPONSE TO NICOTINIC ACID.

This study by researchers at Arena Pharmaceuticals demonstrated that Mattek’s Human Dendritic Cells can be used to identify the mechanism of a drug’s in vivo adverse side effects. Nicotinic acid, used for atherosclerosis treatment, has an adverse effect of skin flushing. The flushing mechanism, thought to be caused by the release of prostaglandin D2 (PGD2), […]

NOREPINEPHRINE INHIBITS LANGERHANS CELL ACTIVATION BY ALTERING CYTOKINE RELEASE.

This study by researchers at Estee Lauder Research Laboratories and Cornell’s Weill Medical College demonstrated that norepinephrine binding to beta adrenergic receptors expressed on the surface of human Langerhans Cells (Mattek’s Human Dendritic Cells) mediated the decrease in immune function by preventing the activation of these immune cells. Psychological stress is potentially harmful to the […]

IMPROVED METHOD FOR THE GENERATION OF LONG LIVED AND FUNCTIONALLY ACTIVE DENDRITIC/LANGERHANS CELLS FROM CD34+ PROGENITOR CELLS.

The difficulty in harvesting large number of cells, short survival time, and rapid phenotypic changes in culture have prevented the widespread use of human dendritic cells (DC)/Langerhans cells (LC) for fundamental studies involving these key immunological cells. Here Mattek scientists report on an improved method of generating DC from CD34+ progenitor cells derived from human […]

PSORIASIN (S100A7) IS A MAJOR ANTIMICROBIAL COMPONENT OF THE FEMALE GENITAL TRACT.

This study by researchers at the Medical University of Vienna and University Hospital Schleswig-Holstein demonstrated that Mattek’s EpiVaginal in vitro 3-D human cervico-vaginal tissue equivalent can be used to confirm psoriasin expression when the tissue was exposed to IL-1alpha and to secreted components of E. coli. Psoriasin has been shown to be the major Escherichia […]

REINFORCEMENT OF INNATE HOST DEFENSE VIA INDUCTION OF ANTI-MICROBIAL PEPTIDES.

Anti-microbial peptides are an important weapon of the innate immune response arsenal. The large surface area of the skin provides an easy target for microbial colonization. Keratinocytes monitor the surface of the skin for potential hazards. When a potential pathogen is encountered, keratinocytes release anti-microbial peptides. We investigated a battery of substances for inducing NHEKs […]

HUMAN β-DEFENSIN-2 PRODUCTION IN KERATINOCYTES IS REGULATED BY INTERLEUKIN-1, BACTERIA, AND THE STATE OF DIFFERENTIATION.

Intact human epidermis resists invasion by pathogenic microbes but the biochemical basis of its resistance is not well understood. Recently, an antimicrobial peptide, human β-defensin-2, was discovered in inflamed epidermis. We used a recombinant baculovirus/insect cell system to produce human β-defensin-2 and confirmed that at micromolar concentrations it has a broad spectrum of antimicrobial activity, […]

CATIONIC POLYPEPTIDES ARE REQUIRED FOR ANTI-HIV-1-ACTIVITY OF HUMAN VAGINAL FLUID.

This study by researchers at the University of Central Florida Biomolecular Science Center demonstrated that Mattek’s EpiVaginal human cervico-vaginal tissue equivalent is an excellent in vitro model for investigating HIV-1 infection via the mucosal surfaces of the vagina, as well as agents that may inhibit/prevent this route of HIV-1 infection, because of the tissue’s ability […]

PLASMACYTOID DENDRITIC CELLS AS A TOOL FOR TESTING ALLERGENICITY OF CHEMICALS.

This study by Mattek Corp. scientists demonstrated that Mattek’s Human Dendritic Cells (DCs) contain both plasmacytoid DCs (pDC) and myeloid DCs (mDC), that they can be separated into those 2 cell populations, and that Mattek pDCs can be used to differentiate between allergens and irritants with a high degree of sensitivity (92-94%) and specificity (93-100%). […]

IMPROVED RESPONSIVENESS OF LANGERHANS / DENDRITIC CELLS TO ALLERGENS.

Langerhans cells (LC) are immature dendritic cells (DC) that are highly specialized antigen-presenting cells (APC) located in the skin, mucosa, and lymphoid tissues. LC play a key role in the induction phase of contact allergenicity, and hence it may be possible to develop an in vitro LC-based assay for contact sensitization. The difficulty in harvesting […]

CHARACTERIZATION AND EVALUATION OF CD34+ GENERATED LANGERHANS CELLS FOR TISSUE ENGINEERING.

Specialized antigen-presenting cells (APC), particularly Langerhans cells (LC) residing in the skin, mucosa, and lymphoid tissues play a key role in sensitization and other immunological reactions of the body. However, difficulty in harvesting, short survival time in culture, and variability in cytokine production of cultured LC has prevented researchers from widespread use of LC for […]

NORMAL HUMAN DENDRITIC CELLS: A TOOL TO STUDY ALLERGIC AND IMMUNOLOGICAL REACTIONS IN VITRO.

Dendritic cells (DC) or Langerhans cells (LC) are immunological cells of the body which play a key role in allergic reactions and infectious diseases. However, widespread experimental use of DC has not occurred since previously-used methods of harvesting DC directly from tissue result in poor yields, short survival time, and rapid phenotypic changes. Currently, we […]

HARVEST, PROLIFERATION, AND FUNCTIONAL TESTING OF HUMAN DENDRITIC CELLS.

Purpose: Difficulty in harvesting large numbers of cells, short survival time, and rapid phenotypic changes in culture have prevented the widespread use of human dendritic cells (DC) for many fundamental studies applicable to the initial stages of pharmaceutical discovery and development. The ability to overcome these problems would enable a broad variety of extremely useful […]