Role of the epidermis and other epithelia in wound healing: Selected concepts

In its normal state, the epidermis is a complex organ in which several cell types, including keratinocytes, Langerhans cells, and melanocytes coexist and interact in complex ways about which little is currently known. The keratinocytes undergo, first, cell division in the deeper layers of the stratum malpighii, then active migration and differentiation to rearrange themselves in the stratum granulosum for final differentiation into keratinized cells. The process by which these cells migrate in an orderly fashion from the undulating dermal-epidermal interface to the flat interface with the keratinized layer is not understood. It is known that few of the basalar cells are undergoing replication at any one time, so that a large, reserve "G^O" pool of cells exists. When there is an injury to the epidermis so that, for example, a portion is removed without damage being done to the dermis, the cell migration pattern changes, so that an increased number of keratinocytes is produced to replace those that have been damaged, killed, or removed. The kinetics of this process is, however, poorly characterized. Also, in states of inflammatory or metabolic injury to the epidermis, there are marked changes, again rather poorly characterized, in epidermal cell migration patterns, which often produce the parakeratotic crust and scale characteristic of many of those pathologic states. Finally, there are diseases-of which the prototype is psoriasis-in which there is a marked change in cellular proliferation and differentiation that, itself, constitutes or produces the major manifestations of the disease. Although the kinetic considerations in psoriasis have been well studied, the studies are difficult to interpret and questions regarding them abound. Recently this problem in nonwounded skin has been reviewed and critically analyzed by Gelfant.¹. We face a large number of uncertainties about the division, migration, and differentiation of keratinocytes in normal, damaged, or pathologically altered epidermis. Further, there are many unanswered questions regarding other epidermal cell types, their interactions with each other and with keratinocytes, and the chemical and other signals that mediate those interactions. Thus, the problem of analyzing the role of the epidermis in wound healing, in which there is damage to the dermis as well as to the epidermis, becomes difficult, if not insolvable. Nevertheless, there are rather extensive experimental data regarding several aspects of the problem, including changes in cell morphology, mechanisms of cell migration, kinetics and patterns of cell migration, and factors controlling cell division. Some of these data on the role of the epidermis in wound healing will now be briefly examined.