USE OF MELANODERM™, AN EPIDERMAL MODEL CONTAINING FUNCTIONAL MELANOCYTES TO STUDY MODULATORS OF SKIN PIGMENTATION.

There is considerable interest in developing both cosmetic and pharma-ceutical formulations which cause darkening or lightening of the skin. These products are utilized to cosmetically alter one’s natural skin color, to provide natural protection from UV irradiation (by increasing melanin content of the skin), or to combat skin pigmentation disorders such as melasma, post-inflammatory hyperpigmentation, and other hyperpigmentation lesions. In order to aid in the development and testing of such products, we have produced MelanoDerm, a highly differentiated, three-dimensional tissue culture model of human epidermis that contains normal human melanocytes (NHM) and keratinocytes (NHK). Using cultures containing NHM from Black (B) donors, the effects of known stimulators of melanogenesis were investigated. Over a three-week period, melanocytes within control cultures remained dendritic but did not significantly increase the bulk pigmentation of the tissue. Experiments using melanocytes derived from Asian (A) and Caucasian (C) donors yielded tissues of varying phototypes with pigmentation levels following the expected order: B > A > C. The addition of 10-7M α-melanocyte stimulating hormone (α-MSH) had little effect on the melanocytes or bulk pigmentation, however 3 ng/ml basic fibroblast growth factor (β-FGF) increased melanocyte number and 10-8M endothelin-1 (EN-1) increased melanocyte dendricity. Both β-FGF and EN-1 increased tissue darkening slightly, however, the combination of β-FGF with either EN-1 or α-MSH dramatically increased the bulk pigmentation of the tissues. In additional experiments, the addition of vitamin D-3 or Stem Cell Factor (SCF) had no effect on the darkening of the tissue. These results suggest that this model will be useful to study melanogenesis, artificial tanning, and other pigmentation phenomena of skin in vitro.

Alpha-MSH (Alpha-melanocyte stimulating hormone), Basic fibroblast growth factor, Beta-FGF (b-FGF), EN-1, Endothelin-1, MSH, MelanoDerm, Melanocyte stimulating hormone, Melanocytes, SCF, Skin pigmentation, Stem cell factor