Modulation of stratum corneum lipid composition and organization of human skin equivalents by specific medium supplements.
Our in-house human skin equivalents contain all stratum corneum (SC) barrier lipid classes, but have a reduced level of free fatty acids (FAs), of which a part is mono-unsaturated. These differences lead to an altered SC lipid organization and thereby a reduced barrier function compared to human skin. In this study, we aimed to improve the SC FA composition and, consequently, the SC lipid organization of the Leiden epidermal model (LEM) by specific medium supplements. The standard FA mixture (consisting of palmitic, linoleic and arachidonic acids) supplemented to the medium was modified, by replacing protonated palmitic acid with deuterated palmitic acid or by the addition of deuterated arachidic acid to the mixture, to determine whether FAs are taken up from the medium and are incorporated into SC of LEM. Furthermore, supplementation of the total FA mixture or that of palmitic acid alone was increased four times to examine whether this improves the SC FA composition and lipid organization of LEM. The results demonstrate that the deuterated FAs are taken up into LEMs and are subsequently elongated and incorporated in their SC. However, a fourfold increase in palmitic acid supplementation does not change the SC FA composition or lipid organization of LEM. Increasing the concentration of the total FA mixture in the medium resulted in a decreased level of very long chain FAs and an increased level of mono-unsaturated FAs, which lead to deteriorated SC lipid properties. These results indicate that SC lipid properties can be modulated by specific medium supplements.
Department of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Varsha S
VS
Thakoersing
Department of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Jeroen
J
van Smeden
Department of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Walter A
WA
Boiten
Department of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Gert S
GS
Gooris
Department of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Aat A
AA
Mulder
Department of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.|Netherlands Metabolomics Centre, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Rob J
RJ
Vreeken
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
Abdoelwaheb
A
El Ghalbzouri
Department of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Joke A
JA
Bouwstra
D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology*; D004537:Eicosanoic Acids / Q000378:metabolism / Q000494:pharmacology; D004817:Epidermis / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes; D050356:Lipid Metabolism / Q000187:drug effects*; D008954:Models, Biological; D019308:Palmitic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012879:Skin Physiological Phenomena / Q000187:drug effects; D017768:Skin, Artificial; D046509:Tissue Culture Techniques
D003470:Culture Media; D004537:Eicosanoic Acids; D005229:Fatty Acids, Monounsaturated; D019308:Palmitic Acid; C094477:arachidic acid
deuterated lipids; fatty acids; lipid organization; skin barrier; stratum corneum