1. Improved organotypic skin model with reduced quantity of monounsaturated ceramides by inhibiting stearoyl-CoA desaturase-1
- Author
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Richard W.J. Helder, G.S. Gooris, Walter A. Boiten, Jannik Rousel, Andreea Nadaban, Abdoelwaheb El Ghalbzouri, and Joke A. Bouwstra
- Subjects
Adult ,Ceramide ,Human skin ,Matrix (biology) ,Ceramides ,Young Adult ,030207 dermatology & venereal diseases ,03 medical and health sciences ,chemistry.chemical_compound ,Organ Culture Techniques ,0302 clinical medicine ,Stratum corneum ,medicine ,Humans ,Enzyme Inhibitors ,Molecular Biology ,Cells, Cultured ,Barrier function ,Skin ,030304 developmental biology ,0303 health sciences ,Corneocyte ,integumentary system ,Chemistry ,Cell Biology ,In vitro ,medicine.anatomical_structure ,Biochemistry ,Female ,lipids (amino acids, peptides, and proteins) ,Stearoyl-CoA desaturase-1 ,Stearoyl-CoA Desaturase - Abstract
Full thickness models (FTM) are 3D in vitro skin cultures that resemble the native human skin (NHS) to a great extent. However, the barrier function of these skin models is reduced. The skin barrier is located in the stratum corneum (SC) and consists of corneocytes embedded in a lipid matrix. In this matrix, deviations in the composition of the FTMs lipid matrix may contribute to the impaired skin barrier when compared to NHS. One of the most abundant changes in lipid composition is an increase in monounsaturated lipids for which stearoyl-CoA desaturase-1 (SCD-1) is responsible. To improve the SC lipid composition, we reduced SCD-1 activity during the generation of the FTMs. These FTMs were subsequently assessed on all major aspects, including epidermal homeostasis, lipid composition, lipid organization, and barrier functionality. We demonstrate that SCD-1 inhibition was successful and resulted in FTMs that better mimic the lipid composition of FTMs to NHS by a significant reduction in monounsaturated lipids. In conclusion, this study demonstrates an effective approach to normalize SC monounsaturated lipid concentration and may be a valuable tool in further optimizing the FTMs in future studies.
- Published
- 2021