Department of Dermatology, VU Medical Center, Amsterdam, The Netherlands.
Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Curr Top Microbiol Immunol. 2021;430:103-129. doi: 10.1007/82_2018_88.
Contact with the skin is inevitable or desirable for daily life products such as cosmetics, hair dyes, perfumes, drugs, household products, and industrial and agricultural products. Whereas the majority of these products are harmless, a number can become metabolized and/or activate the immunological defense via innate and adaptive mechanisms resulting in sensitization and allergic contact dermatitis upon following exposures to the same substance. Therefore, strict safety (hazard) assessment of actives and ingredients in products and drugs applied to the skin is essential to determine I) whether the chemical is a potential sensitizer and if so II) what is the safe concentration for human exposure to prevent sensitization from occurring. Ex vivo skin is a valuable model for skin penetration studies but due to logistical and viability limitations the development of in vitro alternatives is required. The aim of this review is to give a clear overview of the organotypic in vitro skin models (reconstructed human epidermis, reconstructed human skin, immune competent skin models incorporating Langerhans Cells and T-cells, skin-on-chip) that are currently commercially available or which are being used in a laboratory research setting for hazard assessment of potential sensitizers and for investigating the mechanisms (sensitization key events 1-4) related to allergic contact dermatitis. The limitations of the models, their current applications, and their future potential in replacing animals in allergy-related science are discussed.
与皮肤接触是日常生活产品（如化妆品、染发剂、香水、药物、家居产品和工农业产品）所不可避免或期望的。虽然这些产品中的大多数是无害的，但有一些可以通过先天和适应性机制代谢和/或激活免疫防御，从而在随后暴露于同一物质时导致致敏和过敏接触性皮炎。因此，对应用于皮肤的产品和药物中的活性物质和成分进行严格的安全性（危害）评估对于确定 I）该化学物质是否是潜在的致敏物，如果是，则 II）对于人类接触的安全浓度，以防止致敏发生是至关重要的。离体皮肤是皮肤渗透研究的有价值模型，但由于物流和可行性限制，需要开发体外替代物。本综述的目的是清楚地概述目前商业上可获得的或在实验室研究中用于评估潜在致敏物危害以及研究与过敏接触性皮炎相关机制（致敏关键事件 1-4）的器官型体外皮肤模型（重建人表皮、重建人皮肤、包含朗格汉斯细胞和 T 细胞的免疫功能完备的皮肤模型、皮肤芯片）。讨论了模型的局限性、当前应用以及它们在过敏相关科学中替代动物的未来潜力。
