Atopic Dermatitis Studies through In Vitro Models

Abstract

Atopic dermatitis (AD) is a complex inflammatory skin condition that is not fully understood. Epidermal barrier defects and Th2 immune response dysregulations are thought to play crucial roles in the pathogenesis of the disease. A vicious circle takes place between these alterations, and it can further be complicated by additional genetic and environmental factors. Studies investigating in more depth the etiology of the disease are thus needed in order to develop functional treatments. In recent years, there have been significant advances regarding in vitro models reproducing important features of AD. However, since a lot of models have been developed, finding the appropriate experimental setting can be difficult. Therefore, herein, we review the different types of in vitro models mimicking features of AD. The simplest models are two-dimensional culture systems composed of immune cells or keratinocytes, whereas three-dimensional skin or epidermal equivalents reconstitute more complex stratified tissues exhibiting barrier properties. In those models, hallmarks of AD are obtained, either by challenging tissues with interleukin cocktails overexpressed in AD epidermis or by silencing expression of pivotal genes encoding epidermal barrier proteins. Tissue equivalents cocultured with lymphocytes or containing AD patient cells are also described. Furthermore, each model is placed in its study context with a brief summary of the main results obtained. In conclusion, the described in vitro models are useful tools to better understand AD pathogenesis, but also to screen new compounds in the field of AD, which probably will open the way to new preventive or therapeutic strategies.

On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis

“…While in vitro RHE models mimicking disease conditions have frequently been presented in the literature, in most cases their ability to show reversible phenotypes remain to be validated. The aim of this study was to develop a compromised RHE mimicking typical molecular features of AD and to assess its relevance by monitoring the tissue response to molecules known to have beneficial effects on AD‐damaged skin in patients.…”

Skin microbiota and human 3D skin models

“…By removing the apical medium, the keratinocytes are exposed to the air. This triggers the generation and differentiation of several epidermal layers, mimicking a normal differentiated epidermis including the uppermost stratified stratum corneum . In more sophisticated skin equivalents, the keratinocytes are seeded onto a collagen or fibrin matrix containing fibroblasts (Figure B).…”

“…In more sophisticated skin equivalents, the keratinocytes are seeded onto a collagen or fibrin matrix containing fibroblasts (Figure B). In these full‐thickness human skin models, the collagen or fibrin matrix serves as scaffold and mimics the in vivo dermal extracellular matrix.…”

A Quantitative MALDI-MSI Study of the Movement of Molecules in Biological Systems

“…Over the years tissue engineered HSEs have been established as valid models for in-vitro cosmetic and pharmaceutical testing, as well as for the investigation of skin biology mechanisms behind the generation of the epidermis, skin barrier repair/wound healing, skin pathologies and absorption testing (Schäfer-Korting, Mahmoud, et al, 2008;Xie et al, 2010;Ali et al, 2015;De Vuyst et al, 2017;Lewis et al, 2018;Bataillon et al, 2019).…”

“…Chapter 7: Conclusion and future work Conclusion 3D in-vitro tissue models of human skin represent a valid alternative to monolayer 2D cell culture, ex-vivo human and animal skin models, and, at the present time, their application finds a place in many skin research fields (Schäfer-Korting, Mahmoud, et al, 2008;Xie et al, 2010;Ali et al, 2015;De Vuyst et al, 2017;Lewis et al, 2018;Bataillon et al, 2019). 3D in-vitro skin models offer several advantages; they have a higher resemblance to the in-vivo human skin microenvironment compared to monolayer 2D cell culture, they guarantee a higher quality of preservation compared to ex-vivo skin, as they are still living systems they are easy to obtain without requiring an individual ethical licence, and they represent a valid replacement to animal testing in line with the principle of the UK organisation 3Rs (Replacement, Reduction and Refinement).…”