Immune-competent in vitro co-culture models as an approach for skin sensitisation assessment

There is a complex interplay between numerous cell types that act at different steps of the mechanism leading to allergic contact dermatitis. The validated in vitro methods for skin sensitisation assessment provide good statistical correspondence to local lymph node assay (LLNA) or to human data but, for the most part, poorly represent the actual in vivo situation as they generally involve single cell type culture in 2D. Significant progress has been made over the past decades to develop new technologies of data generation concurrently with novel approaches to improve the models especially by the use of co-culture. The importance of heterotypic cell-cell interactions in the in vitro assessment of skin sensitisation should not be overlooked. This review addresses the technical aspects to take into consideration when co-culturing depending on the desired objective and describes the different keratinocytes and dendritic cells co-cultures developed in 2D and 3D. To date, from a regulatory point of view, no alternative method to animal testing for skin sensitisation potential assessment using a keratinocytes and dendritic cells co-culture model is yet proposed. This review also presents several directions of further development.