Contribution of Palmitic Acid to Epidermal Morphogenesis and Lipid Barrier Formation in Human Skin Equivalents

Abstract

The outermost barrier layer of the skin is the stratum corneum (SC), which consists of corneocytes embedded in a lipid matrix. Biosynthesis of barrier lipids occurs de novo in the epidermis or is performed with externally derived lipids. Hence, in vitro developed human skin equivalents (HSEs) are developed with culture medium that is supplemented with free fatty acids (FFAs). Nevertheless, the lipid barrier formation in HSEs remains altered compared to native human skin (NHS). The aim of this study is to decipher the role of medium supplemented saturated FFA palmitic acid (PA) on morphogenesis and lipid barrier formation in HSEs. Therefore, HSEs were developed with 100% (25 μM), 10%, or 1% PA. In HSEs supplemented with reduced PA level, the early differentiation was delayed and epidermal activation was increased. Nevertheless, a similar SC lipid composition in all HSEs was detected. Additionally, the lipid organization was comparable for lamellar and lateral organization, irrespective of PA concentration. As compared to NHS, the level of monounsaturated lipids was increased and the FFA to ceramide ratio was drastically reduced in HSEs. This study describes the crucial role of PA in epidermal morphogenesis and elucidates the role of PA in lipid barrier formation of HSEs.

Advances in generation of three-dimensional skin equivalents: pre-clinical studies to clinical therapies

“…Some studies have reported an altered barrier function in skin equivalents developed in vitro compared with native skin. To counter this, Mieremet et al [36] cultured skin equivalents in the presence of free fatty acids. By supplementing the culture medium of human skin equivalents with palmitic acid (PA), a saturated free fatty acid, the researchers hoped to understand the role of PA on skin morphogenesis and barrier formation.…”

Multitargeted Approach for the Optimization of Morphogenesis and Barrier Formation in Human Skin Equivalents

“…Although CC-FTM(20+) had further reduced levels of muCERs, the lateral organization was similar compared to FTM(20−). This implicates that in CC-FTM, other factors besides reduced monounsaturation could contribute to the formation of the orthorhombic lateral packing, such as a possible increased ratio of FFA to CER [28,[34][35][36]. Future studies should aim to optimize the ratio of CER/FFA/cholesterol in FTMs, which could promote the formation of the orthorhombic lateral packing.…”

A Fatty Acid Fraction Purified From Sea Buckthorn Seed Oil Has Regenerative Properties on Normal Skin Cells

“…However, other FA found in sea buckthorn oil may also contribute to skin health. For example, PA, found in sea buckthorn seeds, is known to be abundant in normal human skin; it contributes to an efficient lipid barrier in in vitro models of skin (Mieremet et al, 2019) and is used by cells as a precursor for longer chain saturated FA. It is being used in skin cosmetic products and considered safe for topic administration.…”