Pigmented human skin equivalent--as a model of the mechanisms of control of cell-cell and cell-matrix interactions.

The melanin pigment system in human skin is extraordinarly well developed and assures the photoprotection of the skin against harmful solar radiation. Specific cell-cell interactions between one melanocytes and keratinocytes play a fundamental role in the regulation of melanogenesis and melanin pigementation, the two key elements of this system, giving rise to the concept of a structural, functional collaborative 'epidermal melanin unit,' Early experiments strongly suggested that melanocyte growth and differentiation are regulated by paracrine factors from keratinocytes and other skin cells. In addition, co-culture studies with keratinocytes has shown that the extracellular matrix acts as a local environmental signal for dendrite formation and melanogenesis. Attempts to reconstruct pigmented human skin in vitro have made great progress over the last decade. The behavior of cells in these pigmented human skin equivalents closely resembles that in vivo, and the cells can still respond to appropriate extrinsic regulatory stimuli such as ultraviolet radiation. Keratinocytes and fibroblasts have been shown to be active partners in the regulation of melanocyte distribution, viability and other differentiation functions, presumably by direct contact and the effects of various soluble paracrine factors. By reproducing cell-cell and cell-matrix interactions, these culture systems provide a promising experimental model for investigating regulation of the skin pigmentary system and the role of photoprotection against harmful solar radiation.