Reconstructed human pigmented skin/epidermis models achieve epidermal pigmentation through melanocore transfer

The skin acts as a barrier to environmental insults and provides many vital functions. One of these is to shield DNA from harmful UV radiation, which is achieved by skin pigmentation arising as melanin is produced and dispersed within the epidermal layer. This is a crucial defence against DNA damage, photoaging and skin cancer. The mechanisms and regulation of melanogenesis and melanin transfer involve extensive crosstalk between melanocytes and keratinocytes in the epidermis and fibroblasts in the dermal layer. Although the predominant means of melanin transfer continues to be debated and several plausible models have been proposed, we and others previously provided evidence for a coupled exo/phagocytosis model. The present study performed histology and immunohistochemistry analyses. It demonstrated a newly developed full-thickness 3D reconstructed human pigmented skin model and an epidermis only model that exhibits dispersed pigment throughout keratinocytes in the epidermis. Furthermore, transmission electron microscopy revealed melanocores between melanocytes and keratinocytes, suggesting that melanin is transferred through coupled exocytosis/phagocytosis of the melanosome core, or melanocore. The study, therefore, presents evidence that in vitro models of pigmented human skin show epidermal pigmentation comparable to human skin. These findings are highly valuable for studies of skin pigmentation mechanisms and pigmentary disorders whilst reducing the reliance on animal models and human skin biopsies.