EFFECTS OF FIBROBLASTS OF DIFFERENT ORIGIN ON LONG-TERM MAINTENANCE OF XENOTRANSPLANTED HUMAN EPIDERMAL-KERATINOCYTES IN IMMUNODEFICIENT MICE

We examined effects of fibroblasts of different origin on long-term ma intenance of xenotransplanted human epidermal keratinocytes. A suspens ion of cultured epidermal cells, originating from adult human trunk sk in, was injected into double mutant immunodeficient (BALB/c nu/scid) m ice subcutaneously, with or without cultured fibroblastic cells of dif ferent origin. At one week after transplantation, the epidermal cells generated epidermoid cysts consisting of human epidermis-like tissue. When the epidermal cells were injected alone or together with fibrobla stic cells derived from human bone marrow, muscle fascia, or murine de rmis, organized epidermoid cysts regressed within 6 weeks. In contrast , when the epidermal cells were injected together with human dermal fi broblasts, generated epidermoid cysts were maintained in vivo for more than 24 weeks. Histological examination showed that the reorganized e pidermis, after injection of both epidermal keratinocytes and dermal f ibroblasts, retained normal structures of the original epidermis durin g 6 to 24 weeks after transplantation. The results indicate that human dermal fibroblasts facilitate the long-term maintenance of the reorga nized epidermis after xenotransplantation of cultured human epidermal keratinocytes by supporting self renewal of the human epidermal tissue in vivo.