RECONSTRUCTED SKIN MODEL CONTAINING LANGERHANS CELLS

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Many highly differentiated in vitro epidermal and dermal/epidermal skin models have been developed, however, none have incorporated immulnologically competent cells such as Langerhans cells (LC). An LC- containing model would be used to study and predict allergic contract dermatitis and hypersensitivity skin reactions. In addition, such a model would find broad application in the immunology field since it is now recognized that epidermal LC play a key role in host defense mechanisms against skin cancer and bacterial, fungal, and viral infections particularly human immunodeficiency virus (HIV). Phase I research will investigate the development of a highly differentiated epidermal model which contains LC, derived from neonatal umbilical cord blood, and keratinocytes, derived from autologous foreskins. LC precursor cells will be harvested, propagated, and matured in vitro, and an effective means of incorporating LC in their native (non-activated) state will be determined. The presence of LC will be verified by immonohistochemistry and quantified using the mixed lymphocyte reaction; ultrastructure will observed using transmission electron microscopy. Finally, functional testing of the model in which the effects of topical applied contact allergens and irritants are compared will probe the utility of the model for studying and predicting contact hypersensitivity. PROPOSED COMMERCIAL APPLICATION: The proposed LC-containing model would reduce or eventually replace the extended and costly sensitization testing done on a myriad of consumer products, chemicals and pharmaceuticals. In addition, it would provide researchers will be valuable immunological tool in studying and developing therapies against skin cancer and bacterial, fungal, and viral infections including HIV.