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Psoriasis is a skin disease characterized by the presence of red plaques on the skin. This pathology is well-known to be a retinoid-sensitive disease. Previous investigations have shown that retinoids can modulate epidermal proliferation with an antiproliferative potential in hyperproliferative skins. The aim of this study was to compare the development of psoriatic substitutes cultured in a retinoic acid supplemented medium with those cultured in medium receiving no supplement, to define the effects of this growth factor on keratinocyte proliferation and differentiation. The self-assembly method was used to create substitutes. Characterization of the psoriatic substitutes was performed by histological and immunolabeling analyses. Results showed that psoriatic keratinocyte substitutes cultured with retinoic acid have a thinner epidermis compared with psoriatic keratinocyte substitutes cultured without this supplement. Further, the expression of all tested cell differentiation markers was restored in psoriatic keratinocyte substitutes cultured in presence of retinoic acid. No significant change in epidermal thickness or in the expression of late differentiation markers was observed in healthy keratinocyte substitutes cultured with or without retinoic acid; however, some changes were reported for proliferation and early differentiation markers. Results suggest that retinoic acid can modulate epidermal differentiation and proliferation with an antiproliferative potential in psoriatic substitutes such as observed in psoriatic skin in vivo.

Summary: Background: Psoriasis is a chronic skin disease characterized by a thickening and disorganization of the skin''s protective barrier. Objectives: This study aims to develop and characterize a novel in vitro psoriatic human skin model produced by tissue engineering. Methods: The self-assembly method, a tissue engineering approach based on the capacity of mesenchymal cells, such as fibroblasts, to create their own extracellular matrix in vitro, was used to create our substitutes. Manipulatable sheets of fibroblasts were superimposed creating a new dermis upon which keratinocytes are seeded, leading to a complete bilayered skin substitute. The characterization of the psoriatic substitutes was performed by macroscopic, histological and immunohistochemical analyses and contrasted to those constructed from healthy cells. Results: Macroscopically, the psoriatic substitutes were more white and thicker than the healthy substitutes. The histological analysis of psoriatic substitutes stained with Masson''s trichrome revealed a characteristic thickening of the epidermal layer seen in psoriatic skin in vivo. Immunohistochemical analysis of the psoriatic substitutes showed, among other things, an overexpression of involucrin and an underexpression of filaggrin and loricrin. Conclusion: These data suggest that the macroscopic, histological and immunohistochemical characteristics of psoriasis are partially retained in the substitutes, thus providing a good model to investigate the mechanisms of abnormal keratinocyte growth and to study cell–cell interactions. [Copyright &y& Elsevier]