The differentiation and proliferation of newly formed epidermis on wounds treated with cultured epithelial allografts

Abstract
Fifteen patients, eight with burn or scald wounds and seven with split-thickness donor sites, were treated with cultured epithelial allografts. Skin was obtained from HIV-negative donors undergoing circumcision and sheets of epithelium were cultured using the 3T3 feeder method. Multiple post-operative biopsies were performed at various time intervals and stained with a panel of monoclonal antibodies against cytokeratins, involucrin, transferrin receptor and epidermal growth factor receptor. Fresh cultured epithelial sheets, normal skin, standard treated donor sites and burns treated with autografts were also studied. Cytokeratin-10 expression was not observed at treated sites until 4 weeks post-grafting, when normal suprabasal levels were observed. Cytokeratins 13 and 16, usually observed in highly proliferative states such as psoriasis, were observed in epithelial-treated sites for up to 6 months. Other proliferation markers such as Ki67 and transferrin receptor were only expressed 2-3 weeks post-operatively. Involucrin, a marker of keratinocyte terminal differentiation, was expressed throughout newly formed epidermis until 15 weeks, when the normal pattern of granular expression was observed. These results indicate that although the cultured 'allograft' does not survive, it may modulate the proliferation and differentiation of spontaneously regenerating epithelium.