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ePaper created 2014-09-15, 12:31:02 | version 1.32.01
Reconstructed Human Skin Equivalents; development and applications Maja Ponec, who was appointed 1969 by Polano to study penetration of corticosteroids through the skin in vitro, started a research line on cultured human keratinocytes to study antiproliferative effects of corticosteroids. Studies with cultured fibroblasts and keratinocytes revealed that glucocorticosteroids inhibit both the cell proliferation and collagen synthesis.[1] Cultured keratinocytes also found clinical applications. In 1985 the first severely burned patients were successfully treated with cultured epidermal sheets.[2] In further studies research focused on generation of a skin substitute with a biodegradable matrix that should provide a support for the epi- dermal cell cultures and function as a scaffold for neodermal regeneration in full-thickness skin loss. More than 25 years ago human skin equivalents (HSEs) were introduced in the research laboratory of the department of dermatology.[3] Such HSEs were generated by seeding human keratinocytes onto a dermal substrate populated with or without fibroblasts. Lifting of the HSEs to the air-liquid interface results in keratinocyte proliferation, differentiation and migration, after which a reconstructed epidermis is formed, closely mimicking the native tissue. As stratum corneum lipids and organization play an important role in the formation of a proper barrier function, extensive studies with advanced techniques in collaboration with Joke Bouwstra at the Leiden/Amsterdam Center for Drug Research (LACDR) have, and are still being performed on this topic. These studies revealed that all lipid classes present in native tissue are also present in HSEs and the supplementation of vitamin C to the culture medium markedly improved barrier function.[4] Studying the barrier function parameters in various keratinization disorders by Sjan Lavrijsen resulted in collaboration with Professor D. Hohl (Lausanne, Switzerland) and contributed to the identification of mutations in lamellar ichthyosis.[5,6] 92 In 2009 Kees Tensen, Abdoel El Ghalbzouri and Suzan Commandeur received the “ZonMw Pearl” of the Netherlands Organisation for Health Research and Development, for their in vitro three-dimensional model of primary human cutaneous squamous cell carcinoma. BWEADVSMGFINCORR:Opmaak 1 21-07-2014 17:40 Pagina 92