Uhm Chanyang, Jeong Haengdueng, Lee Su Hyon, Hwang Jae Sung, Lim Kyung-Min, Nam Ki Taek
Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722 Republic of Korea.
GLP Center, Biosolution Co., Ltd., Seoul, 06746 Republic of Korea.
Toxicol Res. 2023 May 4;39(3):477-484. doi: 10.1007/s43188-023-00185-1. eCollection 2023 Jul.
The Organization for Economic Co-operation and Development approved a reconstructed human epidermis (RHE) model for skin irritation and corrosion tests as an alternative to animal testing for cosmetics, which has been banned in the European Union since 2013. However, RHE models have several limitations, such as high manufacturing costs, a loose skin barrier, and inability to simulate all cellular and non-cellular components of the human epidermis. Therefore, new alternative skin models are needed. Ex vivo skin models have been suggested as promising tools. Here, we investigated the structural similarities in the epidermis of pig and rabbit skin, a commercial RHE model (Keraskin), and human skin. To compare the structural similarity, the thickness of each epidermal layer was compared using molecular markers. Among the candidate human skin surrogates, the epidermal thickness of the pig skin was the most similar to that of human skin, followed by rabbit skin and Keraskin. Keraskin showed thicker cornified and granular layers than human skin, while rabbit skin displayed thinner layers. Moreover, the proliferation indices of Keraskin and rabbit skin were higher than those of human skin, whereas the proliferation index of the pig skin was similar to that of human skin. Some or none of the human skin barrier proteins FLG, CLDN1, and CDH1 were expressed in pig and rabbit skin, whereas all human proteins were expressed in Keraskin. Collectively, we propose ex vivo pig skin as the most suitable model for skin irritation testing because of its similarity to human skin.
The online version contains supplementary material available at 10.1007/s43188-023-00185-1.
经济合作与发展组织批准了一种用于皮肤刺激和腐蚀测试的重组人表皮（RHE）模型，作为化妆品动物测试的替代方法，自2013年起欧盟已禁止化妆品动物测试。然而，RHE模型存在一些局限性，如制造成本高、皮肤屏障疏松以及无法模拟人类表皮的所有细胞和非细胞成分。因此，需要新的替代皮肤模型。体外皮肤模型被认为是有前景的工具。在此，我们研究了猪和兔皮肤、一种商业化RHE模型（Keraskin）以及人类皮肤表皮的结构相似性。为了比较结构相似性，使用分子标记比较了各表皮层的厚度。在候选的人类皮肤替代物中，猪皮肤的表皮厚度与人类皮肤最相似，其次是兔皮肤和Keraskin。Keraskin的角质层和颗粒层比人类皮肤厚，而兔皮肤的这些层较薄。此外，Keraskin和兔皮肤的增殖指数高于人类皮肤，而猪皮肤的增殖指数与人类皮肤相似。猪和兔皮肤中人类皮肤屏障蛋白FLG、CLDN1和CDH1部分表达或不表达，而所有人类蛋白在Keraskin中均有表达。总体而言，我们建议将体外猪皮肤作为皮肤刺激测试最合适的模型，因为它与人类皮肤相似。
在线版本包含可在10.1007/s43188-023-00185-1获取的补充材料。
