Dubau Marla, Tripetchr Tarada, Mahmoud Lava, Schumacher Fabian, Kleuser Burkhard
Freie Universität Berlin, Department of Pharmacology and Toxicology, Institute of Pharmacy, Berlin, Germany.
J Tissue Eng. 2025 May 6;16:20417314251336296. doi: 10.1177/20417314251336296. eCollection 2025 Jan-Dec.
The development of immunocompetent skin models marks a significant advancement in in vitro methods for detecting skin sensitizers while adhering to the 3R principles, which aim to reduce, refine, and replace animal testing. This study introduces for the first time an advanced immunocompetent skin model constructed entirely from induced pluripotent stem cell (iPSC)-derived cell types, including fibroblasts (iPSC-FB), keratinocytes (iPSC-KC), and fully integrated dendritic cells (iPSC-DC). To evaluate the skin model's capacity, the model was treated topically with a range of well-characterized skin sensitizers varying in potency. The results indicate that the iPSC-derived immunocompetent skin model successfully replicates the physiological responses of human skin, offering a robust and reliable alternative to animal models for skin sensitization testing, allowing detection of extreme and even weak sensitizers. By addressing critical aspects of immune activation and cytokine signaling, this model provides an ethical, comprehensive tool for regulatory toxicology and dermatological research.
免疫活性皮肤模型的发展标志着在遵循3R原则（旨在减少、优化和替代动物试验）的体外皮肤致敏剂检测方法方面取得了重大进展。本研究首次引入了一种先进的免疫活性皮肤模型，该模型完全由诱导多能干细胞（iPSC）衍生的细胞类型构建而成，包括成纤维细胞（iPSC-FB）、角质形成细胞（iPSC-KC）和完全整合的树突状细胞（iPSC-DC）。为了评估该皮肤模型的能力，用一系列特征明确、效力不同的皮肤致敏剂对该模型进行局部处理。结果表明，iPSC衍生的免疫活性皮肤模型成功复制了人类皮肤的生理反应，为皮肤致敏试验的动物模型提供了一种强大且可靠的替代方案，能够检测出极强甚至微弱的致敏剂。通过解决免疫激活和细胞因子信号传导的关键问题，该模型为监管毒理学和皮肤病学研究提供了一种符合伦理的综合工具。
