Department of Chemical and Biological Engineer, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110, 8th Street, 12180 Troy, NY, United States; Clinical and Toxicological Analyses Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, Bloco 17, 05508-000 São Paulo, São Paulo, Brazil.
Clinical and Toxicological Analyses Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, Bloco 17, 05508-000 São Paulo, São Paulo, Brazil.
Eur J Pharm Biopharm. 2018 Apr;125:51-57. doi: 10.1016/j.ejpb.2018.01.002. Epub 2018 Jan 6.
Currently, there is a strong global trend towards the development of in vitro models to replace the use of animals in safety evaluation tests. Reconstructed Human Epidermis (RHE) models have been employed as an alternative method to animal testing of skin corrosion and irritation potential of chemical compounds. However, the consequences of an absence of the dermal compartment in these models should be considered since the cross-talk between fibroblasts and keratinocytes is fundamental for promoting proper epidermal stratification, homeostasis, inflammatory response and wound healing. In this study, we compare in-house developed models of Reconstructed Human Epidermis (i.e. USP-RHE) and full thickness skin (i.e. USP-FTS) regarding their response when submitted to skin corrosion assays, based on Guideline 431 (OECD). The results show that both models correctly classified the four substances tested (2-phenylethyl bromide, benzylacetone, lactic acid, octanoic acid) as corrosive or non-corrosive. Furthermore, we have demonstrated higher cell viability of the USP-FTS model compared to the USP-RHE model, a sign of its improved barrier function, following the exposure to the substances test on the corrosion assay. This emphasizes the importance of employing in vitro models that are more physiologically relevant and that better mimic the in vivo situation for the toxicological screening of substances.
目前,全球有一个强烈的趋势,就是开发体外模型来替代动物在安全评估测试中的使用。重建人类表皮(RHE)模型已被用作替代动物测试化合物皮肤腐蚀性和刺激性的方法。然而,由于这些模型中缺乏真皮层,应该考虑其后果,因为成纤维细胞和角质形成细胞之间的串扰对于促进适当的表皮分层、内稳态、炎症反应和伤口愈合是至关重要的。在这项研究中,我们比较了内部开发的重建人类表皮模型(即 USP-RHE)和全厚度皮肤模型(即 USP-FTS),根据 OECD 指南 431,比较它们在皮肤腐蚀性测试中的反应。结果表明,这两种模型都正确地将四种测试物质(2-苯乙基溴、苯乙酮、乳酸、辛酸)分类为腐蚀性或非腐蚀性。此外,我们还证明了与 USP-RHE 模型相比,USP-FTS 模型在暴露于腐蚀性测试中的物质后具有更高的细胞活力,这表明其屏障功能得到了改善。这强调了使用更具生理相关性且更好地模拟体内情况的体外模型对于物质毒性筛选的重要性。