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Kennedy, Alane H.; Golden, Guia M.; Guy, Richard H.; Francoeur, Michael L.; Mak, Vivien H. W.

doi:10.1023/a:1016047816699

Cited by 28 publications

(5 citation statements)

References 28 publications

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“…All these differences were also detected in the previously examined HSEs . Additionally, HSEs developed by other groups or commercially available models also have a reduced SC free fatty acid content, a mainly hexagonal packing and generally show the presence of the LPP . It should be noted that the SC lipid properties of commercially available models were investigated several years ago.…”

Section: Discussionmentioning

confidence: 67%

Nature versus nurture: does human skin maintain its stratum corneum lipid properties in vitro?

Thakoersing

Danso

Mulder

et al. 2012

Experimental Dermatology

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Human skin equivalents (HSEs) mimic human skin closely, but show differences in their stratum corneum (SC) lipid properties. The aim of this study was to determine whether isolation of primary cells, which is needed to generate HSEs, influence the SC lipid properties of HSEs. For this purpose, we expanded explants of intact full thickness human skin and isolated epidermal sheets in vitro. We investigated whether their outgrowths maintain barrier properties of human skin. The results reveal that the outgrowths and human skin have a similar morphology and expression of several differentiation markers, except for an increased expression of keratin 16 and involucrin. The outgrowths show a decreased SC fatty acid content compared with human skin. Additionally, SC lipids of the outgrowths have a predominantly hexagonal packing, whereas human skin has the dense orthorhombic packing. Furthermore, the outgrowths have lipid lamellae with a slightly reduced periodicity compared with human skin. These results demonstrate that the outgrowths do not maintain all properties observed in human skin, indicating that changes in properties of HSEs are not caused by isolation of primary cells, but by culture conditions.

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Section: Discussionmentioning

confidence: 67%

Nature versus nurture: does human skin maintain its stratum corneum lipid properties in vitro?

Thakoersing

Danso

Mulder

et al. 2012

Experimental Dermatology

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“…These factors may be key elements for the decreased permeability barrier observed for LEMs . All HSEs developed so far have a reduced skin barrier function and altered FA content compared to human skin , suggesting that epidermal lipid metabolism is partially disturbed in all these models.…”

Section: Discussionmentioning

confidence: 99%

Modulation of stratum corneum lipid composition and organization of human skin equivalents by specific medium supplements

Thakoersing

Smeden

Boiten

et al. 2015

Experimental Dermatology

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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.

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“…Mak et al demonstrated that de-epidermized dermis coupled with 1,25-dihydroxy vitamin D3 helps the barrier resemble that of human skin ( Mak et al, 1991 ). Even still, this model lacked covalently bound lipid lamellae that properly extruded into the regions between cells, which is a foundational part of the skin barrier ( Bouwstra et al, 1995 ; Kennedy et al, 1996 ). Following this, Boyce and Williams showed that adding palmitic acid, essential fatty acids, and antioxidants increased the synthesis of lipids and improved extrusion ( Boyce and Williams, 1993 ).…”

Section: Discussionmentioning

confidence: 99%

In vitro percutaneous penetration test overview

Shahinfar

Maibach

2023

Front. Pharmacol.

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Skin is a detailed, organized, and intricate niche in the human body. Topical and transdermal drugs are unique, in that their absorption is quite different from other routes of administration (oral, intramuscular, intravenous, etc.,.). A robust amount of research is required to approve the use of a drug—in vivo, in vitro, and ex vivo studies collectively help manufacturers and government agencies with approval of various compounds. Use of human and animal studies poses ethical and financial concerns, making samples difficult to use. In vitro and ex vivo methods have improved over the past several decades—results show relevance when compared to in vivo methods. The history of testing is discussed, followed by a detailed account of known complexities of skin and the current state of percutaneous penetration.

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Abstract: The profound differences in SC lipid composition, organization and conformational properties attest that permeability alone is not a sufficiently sensitive marker to define barrier equivalence between cultures and human skin.

Cited by 28 publications

References 28 publications

Nature versus nurture: does human skin maintain its stratum corneum lipid properties in vitro?

Nature versus nurture: does human skin maintain its stratum corneum lipid properties in vitro?

Modulation of stratum corneum lipid composition and organization of human skin equivalents by specific medium supplements

In vitro percutaneous penetration test overview

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