The epidermis is composed of closely packed cells with very little intercellular matrix. Most of epidermal cells are keratinocytes which synthesize keratin and are eventually lost by desquamation. This loss is compensated by permanent proliferation of basal cells so that the biology of living epidermis is dominated by keratinization and regulation of growth. Mainly 2 mechanisms have been proposed for this regulation. The first is based on the fact that the epidermis is always in contact with the underlying dermis. The idea is that growth as well as keratinization are controlled by connective tissue factors passing through the basement membrane. According to the second, signals are emitted by maturing, keratinizing cells, which control the activity of basal cells by blocking them at various stages along the cell cycle. One major point in using epidermal cell cultures as models for living epidermis is to isolate epidermal cells to eventually study the various factors influencing their growth at the molecular level. Besides keratinocytes there are other epidermal cells such as melanocytes and Langerhans cells. But in contrast to keratinocytes which accomplish their biological function (keratinization) independently of other cell types, the functions of melanocytes and Langerhans cells are more or less dependent upon their interactions with adjacent keratinocytes with which they form some sort of epidermal 'symbionts'. For example skin pigmentation is largely influenced by interactions between melanocytes and keratinocytes. Also, contacts between these latter cells and Langerhans cells are important in epidermal immunology. Thus, the epidermis is a complex tissue, the biology of which rests not only on that of the keratinocyte taken as a separate element, but also on the interactions that it (the keratinocyte) has with other epidermal cells. Consequently, when epidermal cell cultures are considered as models for living epidermis at least 2 types of culture systems must be envisaged: one for the study of the biology of keratinocytes, proper, and one for that of keratinocytic-nonkeratinocytic cell interactions. In addition, living epidermis is morphologically organized. The proliferative compartment is composed of basal cells which appear like a palisade on vertical histology sections whereas the maturing compartment is made of flattened cells which pile up into adjacent columns. This raises the question as to whether epidermal morphogenesis can be approached through tissue culture methods. Finally, living epidermis can regenerate after wounding and, here again the question is to see if regeneration can be studied in culture.
