MatTek Corporation, 200 Homer Avenue, Ashland, MA 01721, USA.
The Procter & Gamble Company, Mason Business Center, Cincinnati, OH 45040, USA.
J Dermatol Sci. 2014 Mar;73(3):187-97. doi: 10.1016/j.jdermsci.2013.11.004. Epub 2013 Nov 11.
Barrier function is integral to the health of epithelial tissues. Currently, there is a broad need to develop and improve our knowledge with regard to barrier function for reversal of mild skin irritation and dryness. However, there are few in vitro models that incorporate modulations of both lipids and epidermal differentiation programs for pre-clinical testing to aid in the understanding of barrier health.
We have generated a reconstituted epidermis on a decellularized dermis (DED) and characterized its barrier properties relative to human epidermis in order to determine its utility for modeling barrier formation and repair.
We followed the process of epidermal differentiation and barrier formation through immunocytochemistry and transcriptional profiling. We examined barrier functionality through measurements of surface pH, lipid composition, stratum corneum water content, and the ability to demonstrate topical dose-dependent exclusion of surfactant.
Transcriptional profiling of the epidermal model during its formation reveals temporal patterns of gene expression associated with processes regulating barrier function. The profiling is supported by gradual formation and maturation of a stratum corneum and expression of appropriate markers of epidermis development. The model displays a functional barrier and a water gradient between the stratum corneum and viable layers, as determined by confocal Raman spectroscopy. The stratum corneum layer displays a normal acidic pH and an appropriate composition of barrier lipids.
The epidermal model demonstrates its utility as an investigative tool for barrier health and provides a window into the transcriptional regulation of multiple aspects of barrier formation.
屏障功能是上皮组织健康的重要组成部分。目前，广泛需要发展和提高我们对屏障功能的认识，以逆转轻度皮肤刺激和干燥。然而，很少有体外模型可以同时调节脂质和表皮分化程序，用于临床前测试，以帮助理解屏障健康。
我们已经在脱细胞真皮（DED）上生成了一个重建的表皮，并对其屏障特性进行了表征，以便确定其在建模屏障形成和修复方面的适用性。
我们通过免疫细胞化学和转录谱分析来跟踪表皮分化和屏障形成的过程。我们通过测量表面 pH 值、脂质组成、角质层水分含量以及展示表面活性剂局部剂量依赖性排斥的能力来检查屏障功能。
在表皮模型形成过程中的转录谱分析揭示了与调节屏障功能的过程相关的基因表达的时间模式。该分析得到了逐渐形成和成熟的角质层以及表皮发育适当标志物表达的支持。该模型显示出功能性屏障和角质层与活层之间的水分梯度，这是通过共聚焦拉曼光谱确定的。角质层显示出正常的酸性 pH 值和适当的屏障脂质组成。
表皮模型证明了其作为屏障健康研究工具的实用性，并为多个方面的屏障形成的转录调节提供了一个窗口。
