RECONSTRUCTION OF SKIN MODEL CONTAINING LANGERHANS CELLS
DESCRIPTION (provided by applicant): Phase I research demonstrated that a Langerhans cell (LC) containing model of the epidermis is feasible. LC progenitor cells were harvested from peripheral or cord blood samples, cryopreserved, and matured using cytokines into the LC specific CD1a+ phenotype. By modifying the extracellular matrix substrate, these cells were successfully incorporated into a highly differentiated, serum-free epidermal model, albeit at a lower density than in native epidermis. The LC derived from cord blood maintained their dendntic, CD1a+ HLA-DR+/- phenotype and expressed Birbeck granules within the cultures. The exposure of 2 contact allergens resulted in the release of TNF-a and IL-lb. 2 cytokines known to be critically involved in the initial stages of allergic contact dermatitis (ACD). Exposure to the common irritant, on the other hand, did not result in TNF-a or IL- lb release. In addition, following exposure to UV irradiation, immuno-staining showed that LC were migrating out of the tissue, as is known to occur in vivo.Phase II studies will expand on the Phase I results to further develop an epidermal model containing immunologically competent cells. Initial research will focus on the optimization of culture conditions to improve LC incorporation into the tissue model. The effects of allergens on cytokine release and gene expression will be investigated. Experiments designed to model LC migration from skin following exposure to allergens or UV light and subsequent T-cell activation will be performed to determine the degree to which the model's behavior corresponds to in vivo ACD reactions. Finally, based on these studies, an assay kit to predict whether a material is likely to act as a contact allergen will be developed.
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