Development of an iPSC-derived immunocompetent skin model for identification of skin sensitizing substances

Abstract

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.