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Epidermal keratinocyte self-renewal is dependent upon dermal integrity.

The epidermis is a major site of self-renewal in which there is constant replacement by cell division in the basal layers of cells lost by desquamation in the superficial layers. Such a tissue is therefore likely to contain stem cells and in this study we have examined the role of the dermis in the maintenance of epidermal self-renewal. We have developed a mouse model to address the question of whether the maintenance of epidermal self-renewal is dependent, as in the hemopoietic system, upon a heterologous cell type. Intact epidermis separated from dermis at the dermo-epidermal junction or epidermis derived from disaggregated epidermal cells, can reconstitute a stratified squamous epithelium when grafted onto the lumbo-dermal fascia of the mouse or onto an experimentally induced granulation tissue bed. However, we have shown that, after grafting, the clonogenic capacity of the keratinocytes declines sharply and the colonies that are produced are incapable of self-renewal in vitro. Although initially hyperplastic, these epidermal grafts assume an atrophic appearance after 40-70 d and this may be related to the loss of self-renewal observed in vitro. With both experimental murine grafts and clinical grafts the failure of keratinocytes to self-renew can be alleviated, partially, by the presence of the dermis in full-thickness or split-thickness grafts, which implies that the dermis has a functional role in epidermal stem cell maintenance. The relevance of these observations to the clinical experience with cultured autologous keratinocyte sheets as wound dressings to patients is discussed.