scholarly journals 334 Impact of injury-induced inflammation on ex vivo skin culture as a preclinical model for atopic dermatitis

2020 ◽  
Vol 140 (7) ◽  
pp. S41
Author(s):  
H. Zhou ◽  
S. Engle ◽  
C. Chang ◽  
M. Daniels ◽  
A.J. Okragly ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
Preclinical Model ◽  
Skin Culture

scholarly journals Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for atopic dermatitis (AD) treatment

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Audrey Baylet ◽  
Raoul Vyumvuhore ◽  
Marine Laclaverie ◽  
Laëtitia Marchand ◽  
Carine Mainzer ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
Topical Therapy ◽  
Human Keratinocytes ◽  
Raman Microspectroscopy ◽  
Interleukin 4 ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Administration Routes

AbstractCurrently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin. The aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4). Transcutaneous penetration was evaluated by ex vivo studies on tape-stripped pig ear skin. ScFv and Ab visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied in vitro using HEK-Blue™ IL-4/IL-13 cells and normal human keratinocytes (NHKs). After 24 h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on the stratum corneum. In addition, the anti-hIL4 scFv showed very efficient and dose-dependent hIL-4 neutralization. Thus, scFv penetrates through to the upper papillary dermis while Ab mostly remains on the surface, the anti-hIL4 scFv also neutralizes its target effectively suggesting its potential use as topical therapy for AD.

scholarly journals Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for Atopic Dermatitis (AD) treatment

2021 ◽  
Author(s):  
Audrey Baylet ◽  
Raoul Vyumvuhore ◽  
Marine Laclaverie ◽  
Laëtitia Marchand ◽  
Carine Mainzer ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
Topical Therapy ◽  
Human Keratinocytes ◽  
Raman Microspectroscopy ◽  
Poly I:C ◽  
Interleukin 4 ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Polycytidylic Acid

SummaryBackgroundCurrently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis (PSO) or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin.ObjectivesThe aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4).MethodsTranscutaneous penetration was evaluated by ex vivo studies on tape-stripped pig ear skin. Antibody visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied using two 2D models. First, embryonic alkaline phosphatase (SEAP) secretion by HEK-Blue™ IL-4/IL-13 cells, proportional to hIL-4 cells stimulation, was quantified by OD 620 nm measurement in presence or absence of an anti-hIL4 scFv or Ab. Then, normal human keratinocytes (NHKs) were stimulated with polyinosinic-polycytidylic acid (poly I:C) +/− hIL-4 and treated with anti-hIL4 scFv. Human Interleukin-8 (hIL-8) concentrations were determined in culture supernatants by ELISA.ResultsAfter 24h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on the stratum corneum. In addition, the anti-hIL4 scFv showed better efficiency compared to Ab, with a neutralization percentage at 200 nM of 68% and 47%, respectively, in the HEK-Blue™ IL-4/IL-13 model. hIL-8 dosage in stimulated NHKs supernatants revealed that addition of scFv induced a dose-dependent hIL-4 neutralization.ConclusionsscFv penetrates through to the upper papillary dermis while Ab remains on the surface. The anti-hIL4 scFv neutralizes its target effectively in two 2D models suggesting its potential use as topical therapy for AD.

scholarly journals Topical Pioglitazone Nanoformulation for the Treatment of Atopic Dermatitis: Design, Characterization and Efficacy in Hairless Mouse Model

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 255 ◽  
Author(s):  
Lupe Carolina Espinoza ◽  
Rodrigo Vera-García ◽  
Marcelle Silva-Abreu ◽  
Òscar Domènech ◽  
Josefa Badia ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Skin Barrier ◽  
Inflammatory Cells ◽  
Hairless Mouse ◽  
Skin Barrier Function ◽  
Inflammatory Parameters ◽  
Therapeutic Benefits

Pioglitazone (PGZ) is a drug used to treat type 2 diabetes mellitus that has been reported to show additional therapeutic activities on diverse inflammatory parameters. The aim of this study was to optimize a topical PGZ-loaded nanoemulsion (PGZ-NE) in order to evaluate its effectiveness for treating atopic dermatitis (AD). The composition of the nanoformulation was established by pseudo-ternary diagram. Parameters such as physical properties, stability, in vitro release profile, and ex vivo permeation were determined. The efficacy study was carried out using oxazolone-induced AD model in hairless mice. PGZ-NE released the drug following a hyperbolic kinetic. Additionally, its properties provided high retention potential of drug inside the skin. Therapeutic benefits of PGZ-NE were confirmed on diverse events of the inflammatory process, such as reduction of lesions, enhancement of skin barrier function, diminished infiltration of inflammatory cells, and expression of pro-inflammatory cytokines. These results were reinforced by atomic force microscope (AFM), which demonstrated the ability of the formulation to revert the rigidification caused by oxazolone and consequently improve the elasticity of the skin. These results suggest that PGZ-NE may be a promising treatment for inflammatory dermatological conditions such as AD.

scholarly journals 932 Development of an early wound model in human ex vivo skin explant as a preclinical model of wound healing

2019 ◽  
Vol 139 (5) ◽  
pp. S161
Author(s):  
A.V. Caserta ◽  
J.E. Neil ◽  
J. Volmer ◽  
L. Ring ◽  
J. Lenn ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Preclinical Model ◽  
Wound Model ◽  
Early Wound

scholarly journals Micron-sized and submicron-sized aerosol deposition in a new ex vivo preclinical model

2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Sophie Perinel ◽  
Lara Leclerc ◽  
Nathalie Prévôt ◽  
Agathe Deville ◽  
Michèle Cottier ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aerosol Deposition ◽  
Preclinical Model

scholarly journals Clumping Factor B Promotes Adherence of Staphylococcus aureus to Corneocytes in Atopic Dermatitis

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Orla M. Fleury ◽  
Maeve A. McAleer ◽  
Cécile Feuillie ◽  
Cécile Formosa-Dague ◽  
Emily Sansevere ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Clonal Complex ◽  
Ex Vivo ◽  
Nasal Carriage ◽  
Binding Activity ◽  
Clinical Strain ◽  
Healthy Children ◽  
Content Type ◽  
Force Microscopy

ABSTRACT Staphylococcus aureus skin infection is a frequent and recurrent problem in children with the common inflammatory skin disease atopic dermatitis (AD). S. aureus colonizes the skin of the majority of children with AD and exacerbates the disease. The first step during colonization and infection is bacterial adhesion to the cornified envelope of corneocytes in the outer layer, the stratum corneum. Corneocytes from AD skin are structurally different from corneocytes from normal healthy skin. The objective of this study was to identify bacterial proteins that promote the adherence of S. aureus to AD corneocytes. S. aureus strains from clonal complexes 1 and 8 were more frequently isolated from infected AD skin than from the nasal cavity of healthy children. AD strains had increased ClfB ligand binding activity compared to normal nasal carriage strains. Adherence of single S. aureus bacteria to corneocytes from AD patients ex vivo was studied using atomic force microscopy. Bacteria expressing ClfB recognized ligands distributed over the entire corneocyte surface. The ability of an isogenic ClfB-deficient mutant to adhere to AD corneocytes compared to that of its parent clonal complex 1 clinical strain was greatly reduced. ClfB from clonal complex 1 strains had a slightly higher binding affinity for its ligand than ClfB from strains from other clonal complexes. Our results provide new insights into the first step in the establishment of S. aureus colonization in AD patients. ClfB is a key adhesion molecule for the interaction of S. aureus with AD corneocytes and represents a target for intervention.

scholarly journals Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1237
Author(s):  
Thomas Bauer ◽  
Daniela Gubi ◽  
Jörg Klufa ◽  
Philipp Novoszel ◽  
Martin Holcmann ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
The Body ◽  
Suitable Model ◽  
Ex Vivo Model ◽  
Egfr Inhibition ◽  
Explant Cultures ◽  
Barrier Immunity

The skin is the outermost barrier protecting the body from pathogenic invasion and environmental insults. Its breakdown initiates the start of skin inflammation. The epidermal growth factor (EGFR) on keratinocytes protects this barrier, and its dysfunction leads to atopic dermatitis-like skin disease. One of the initial cytokines expressed upon skin barrier breach and during atopic dermatitis is TSLP. Here, we describe the expression and secretion of TSLP during EGFR inhibition and present an ex-vivo model, which mimics the early events after barrier insult. Skin explants floated on culture medium at 32 °C released TSLP in parallel to the activation of the resident Langerhans cell network. We could further show the up-regulation and activation of the AP-1 family of transcription factors during atopic-like skin inflammation and its involvement in TSLP production from the skin explant cultures. Inhibition of the c-Jun N-terminal kinase pathway led to a dose-dependent blunting of TSLP release. These data indicate the involvement of AP-1 during the early stages of atopic-like skin inflammation and highlight a novel therapeutic approach by targeting it. Therefore, skin explant cultures mimic the early events during skin barrier immunity and provide a suitable model to test therapeutic intervention.

scholarly journals Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pauliina M. Munne ◽  
Lahja Martikainen ◽  
Iiris Räty ◽  
Kia Bertula ◽  
Nonappa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Therapeutic Interventions ◽  
Preclinical Model ◽  
Matrix Stiffness ◽  
Breast Cancers ◽  
Ex Vivo Model ◽  
Major Barrier ◽  
The Matrix

AbstractBreast cancer is now globally the most frequent cancer and leading cause of women’s death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα + ) phenotype that is initially responsive to antihormonal therapies, but drug resistance emerges. A major barrier to the understanding of the ERα-pathway biology and therapeutic discoveries is the restricted repertoire of luminal ERα + breast cancer models. The ERα + phenotype is not stable in cultured cells for reasons not fully understood. We examine 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. Matrix stiffness upregulates the ERα signaling via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. Subject terms: ER-positive (ER + ), breast cancer, ex vivo model, preclinical model, PDEC, stiffness, p38 SAPK.

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