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Current status of healthy human skin models: can histone deacetylase inhibitors potentially improve the present
M Lemper1, S Snykers, T Vanhaecke
1Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Belgium.
Abstract:
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.
Insights
Histone deacetylase inhibitors (HDACi) impact skin cell morphology and differentiation. These epigenetic agents may offer new avenues for developing and studying human skin models.
Area of Science:
- Dermatology
- Epigenetics
- Cell Biology
Background:
- Histone deacetylase inhibitors (HDACi) are epigenetic agents with demonstrated antiproliferative and prodifferentiation effects in cancer cell lines.
- Understanding HDACi effects on normal cells is crucial for tissue homeostasis and evaluating new chemical entities.
- Limited data exists on HDACi's impact on healthy human skin physiology.
Purpose of the Study:
- To review the effects of HDACi on healthy human primary skin cell cultures.
- To examine HDACi's influence on three-dimensional epidermal models.
- To consolidate current knowledge on HDACi's impact on normal skin.
Main Methods:
- Literature review of studies investigating HDACi effects on human skin cells.
- Analysis of data from in vitro experiments using primary skin cell cultures.
- Evaluation of findings from three-dimensional epidermal models treated with HDACi.
Main Results:
- HDACi influence both epidermal morphology and the differentiation process in human skin.
- Observed effects include cell cycle arrest, basal layer disorganization, stratum spinosum thinning, and stratum corneum thickening.
- Cytoskeletal reorganization and increased cornified envelope formation were noted.
Conclusions:
- HDACi significantly affect human skin cell morphology and differentiation.
- Despite limited research, HDACi show potential as tools for developing and studying novel human skin models.
- Further investigation into HDACi's effects on healthy skin is warranted.
