Wound healing of human skin transplanted onto the nude mouse: II. An immunohistological and ultrastructural study of the epidermal basement membrane zone reconstruction and connective tissue reorganization

The reconstruction of human epidermis during healing of human skin wounded after grafting onto the nude mouse was described in a previous paper ( M. Démarchez, P. Sengel, and M. Pruniéras, 1986, Dev. Biol. 113, 90–96 ). The regeneration of the epidermal basement membrane zone (BMZ) and the reorganization of the connective tissue are the subjects of the present study. They were investigated by two complementary methods: (1) electron microscopy to analyze the BMZ reorganization, and (2) indirect immunofluorescence with species-specific and cross-reacting antibodies directed against laminin, bullous pemphigoid antigen, mouse or human collagens of types I or IV, human elastic fibers, fibronectin, fibrin, actin, and human vimentin, to examine the species origin and distribution of BMZ and connective tissue components during the regeneration process. It is reported that grafted human skin preserves its own immunological markers not only in the epidermis but also in the BMZ and dermis as well, and that, after injury, its regeneration proceeds according to the following sequence of overlapping events: (1) production of a mouse granulation tissue; (2) reepidermization by human cells; (3) reconstruction of a BMZ with human characteristics; (4) formation of a human neodermis. It is concluded that human skin grafted onto the nude mouse is able to regenerate its three structural compartments, namely, the epidermis, BMZ, and dermis. Interestingly, it appeared, also, that the connective tissue regeneration would be a two-step mechanism including the sequential formation of two tissues of distinct sources, namely, a granulation tissue and a neodermis.