Current status of healthy human skin models: can histone deacetylase inhibitors potentially improve the present replacement models?
Histone deacetylase inhibitors (HDACi), a relatively new group of epigenetic agents, are being investigated as powerful chemotherapeutics because of their antiproliferative and prodifferentiation effects both in vitro and in vivo, in various tumor cell lines. Only little is known with respect to their effects on normal cells. Yet, to understand tissue pathology and evaluate potential effects of new chemical entities in tissue homeostasis, insight into the physiology of healthy tissue is necessary. Therefore, this review addresses the effects of HDACi on healthy human primary skin cell cultures and three-dimensional epidermal models. In general, HDACi exert an effect on both the epidermal morphology and differentiation process of human skin. The latter is manifested through cell cycle arrest, disorganization of the basal layer, thinning of the stratum spinosum and thickening of the stratum corneum, reorganization of the cytoskeleton and increased formation of cornified envelopes. This overview shows that, although only a limited number of reports exist, these molecules might be an interesting tool for the development and study of new human skin models.
Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Belgium.
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M
Lemper
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Snykers
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Vanhaecke
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De Paepe
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V
Rogiers
D000107:Acetylation; D000826:Animal Testing Alternatives; D002478:Cells, Cultured; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D046509:Tissue Culture Techniques; D023822:Tissue Engineering
D056572:Histone Deacetylase Inhibitors; D006657:Histones