ORGANOTYPIC SKIN MODELS CONTAINING MELANOCYTES

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Phase I research demonstrated that normal human melanocytes could be directly added to a highly differentiated, serum-free tissue culture model of the human epidermis. The melanocytes incorporated therein retained their highly dendritic nature and were localized within the basal cell layer of the tissue culture construct. The substrate, I-dopa, was converted to melanin and ultrastructural analysis revealed the presence of numerous melanosomes contained within the melanocytes, some of which were transferred to adjacent keratinocytes. Finally, initial characterization of the model showed that the melanocytes did not deleteriously affect any of the advantageous properties of the epidermal model. Phase II research will build on the Phase I results to further develop the three-dimensional, melanocyte-containing tissue models into accurate, useful, and commercially viable products. Initial studies will probe potential nutritional or hormonal deficiencies which may be present in the culture medium. The choice of melanocytes and the handling thereof in culture will also be optimized. Further characterization of the model~s properties, particularly those which will be affected be exposure to ultraviolet irradiation (UV), along with the model~s reproducibility, will be studied. In addition, the accuracy of the model will be probed using exogenous stimuli to melanogenesis. Finally, the use of melanocytes obtained from vitiliginous skin will represent the first three-dimensional model of this relatively common skin disorder. It is believed that such tissue constructs will help elucidate some of vitiligo~s underpinnings which currently are not understood. PROPOSED COMMERCIAL APPLICATION The proposed research will lead to commercially viable, melanocyte- containing skin models which will assist companies in developing products which affect, or are affected by, skin pigmentation. The skin models will find utility in understanding melanogenesis and modulators thereof, studying skin pigmentation disorders, and elucidating mechanisms of UV light induced damage to the epidermis. In addition, the vitiligo tissue constructs will assist dermotologic companies in developing pharmaceuticals and /or therapies to treat to this widespread skin pigmentation disease.