Full-Thickness Human Skin Equivalent Models of Atopic Dermatitis
Atopic dermatitis is a chronic inflammatory skin disease caused by complex multifactorial etiology. In the recent years, there have been significant advances in tissue engineering and the generation of in vitro skin models representative of healthy and diseased states. This chapter describes the methodology for the fabrication of in vitro human skin equivalent (HSE) from human keratinocytes and fibroblasts using a fibrin-based dermal matrix and serum-free culture conditions. Modification of the culture conditions with the supplementation of Th2 cytokines such as interleukin-4 induces the development of atopic dermatitis-like skin model. The chapter also describes the histological and immunohistochemical tools for characterization of the HSE model. The reconstruction of tissue-engineered HSE models that recapitulate the essential features of atopic dermatitis provides powerful tools for deeper understanding of the underlying pathological mechanisms on epidermal level, identification and testing of novel treatment options, and safety and toxicological evaluation in a pathophysiologically relevant system.
Keywords3D tissue constructs Atopic dermatitis Fibrin Full-thickness Human skin equivalent Organoids Organotypic culture Tissue engineering
This work was partially supported by grants from Singapore Ministry of Education, NUS Start Up Grant (R221000118133) to G.S., and A*STAR’s Joint Council Office grant, Singapore [1334K00081] to P.L.B., and M.B. The authors thank Dr. J. Rheinwald (Harvard Medical School, Boston, MA) for his kind gift of immortalized human N/TERT-1 keratinocytes. The authors thank Skin Bank, Institute of Medical Biology, A*STAR for provision of human primary foreskin-derived dermal fibroblasts.
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