Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Comparison of structural characteristics and molecular markers of rabbit skin, pig skin, and reconstructed human epidermis for an ex vivo human skin model

  • Chanyang Uhm (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Haengdueng Jeong (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Su Hyon Lee (GLP Center, Biosolution Co., Ltd.) ;
  • Jae Sung Hwang (Genetics and Biotechnology, College of Life Science, Kyung Hee University) ;
  • Kyung‑Min Lim (College of Pharmacy, Ewha Womans University) ;
  • Ki Taek Nam (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine)
  • Received : 2023.02.08
  • Accepted : 2023.04.19
  • Published : 2023.07.15
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Abstract

The Organization for Economic Co-operation and Development approved a reconstructed human epidermis (RHE) model for in vitro 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.

Keywords

Acknowledgement

This study was part of a cosmetic safety evaluation project carried out by the Korea Cosmetic Industry Institute (KCII), funded by the Ministry of Health and Welfare, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant No. HP20C0061). This study was also supported by the Korea Mouse Phenotyping Project NRF-2016M3A9D5A01952416 National Research Foundation (NRF) grant funded by the Korean government (Ministry of Science, ICT and Future Planning) (KTN) and NRF of Korea grant 2022R1A2C3007850 (KTN).

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