Ex vivo human skin model as a tool for atopic dermatitis assessment.
Author: Samara Eberlin
Published at: November 13, 2020
American Academy of Dermatology Annual Meeting AAD, Denver-CO, USA. March 20th-24th, 2020.
Samara Eberlin, Gustavo Facchini, Michelle Sabrina da Silva, Gustavo Henrique da Silva, Ana Lúcia Tabarini Alves Pinheiro, Adilson Costa.
Atopic dermatitis (AD) is a chronically relapsing inflammatory disease associated with genetic predisposition and environmental factors. Altered immune response and skin barrier dysfunction are mainly responsible for skin lesion onset characterized by severe itching. Affected patients are highly sensitized to house dust mite, such as Dermatophagoides farinae (DF), which is considered a common environmental allergen causing AD. Among the abnormalities in the epidermal barrier, changes in lipid profile of stratum corneum are highlighted, with the most notable feature being the decrease in ceramide levels. Additionally, there is a reduction in the levels of envelope proteins filaggrin, involucrin, and loricrin. An ex vivo AD model was developed using skin fragments obtained from elective plastic surgery and submitted to epidermal barrier disruption with 4% sodium lauryl sulfate. Complementary, the skin was exposed to DF extract for two consecutive days. Skin fragments were collected, fixed, and cryopreserved for immunofluorescence evaluation of filaggrin, involucrin, loricrin, and sphingomyelin synthase. Our results revealed that the human experimental AD model was able to satisfactorily mimic skin characteristics of AD by significantly reducing filaggrin, involucrin, and loricrin labeling when compared to the control group. Labeling for sphingomyelin synthase - which is directly related to ceramide synthesis, also dropped considerably. Fragments of ex vivo human skin constitute the experimental model that most closely approximates the real conditions to evaluate the efficacy and safety of products applied topically. These findings strongly suggest that this model can be useful not only for elucidating AD pathogenesis but also for evaluating novel therapeutic agents.