THE FETAL FIBROBLAST - THE EFFECTOR CELL OF SCARLESS FETAL SKIN REPAIR

Human fetal skin heals without scar formation when it is transplanted to a subcutaneous location on an adult athymic mouse and subsequently wounded. In contrast, human fetal skin of identical gestational age he als with scar formation when transplanted to a cutaneous location on t he athymic mouse recipient To determine if mouse (adult) or human (fet al) fibroblasts are healing the graft wounds, we performed indirect im munohistochemistry for mouse and human collagen types I and III. Full- thickness skin g-rafts (n = 51) from human fetuses at 18 weeks' (n = 4 ) or 24 weeks' (n = 2) gestational age were placed onto athymic mice i n two locations: cutaneously onto a fascial bed and subcutaneously in a pocket under the murine panniculus carnosus. Linear incisions were m ade in each graft 7 days after transplantation. Grafts were harvested at 7, 14, and 21 days after wounding and stained with hematoxylin and eosin or Mallory's trichrome. Immunohistochemistry for either human co llagen type I or type III or for mouse collagen type I was performed. The subcutaneous grafts healed with human collagen types I and III in a scarless pattern. The wound collagen pattern was reticular and unrec ognizable from the surrounding dermis. Hair follicles and sebaceous gl and patterns were unchanged in the wounded dermis. Conversely, the cut aneous grafts healed with mouse collagen in a scar pattern with disorg anized collagen fibers and no appendages. Mouse collagen scar was pres ent along the base of the cutaneous grafts and as a thin capsule aroun d the subcutaneous grafts. We conclude that (1) subcutaneous grafts he al with human fetal collagen and no scar formation, and (2) cutaneous grafts heal with mouse collagen in a scar pattern. Fetal fibroblasts c an heal fetal skin wounds without scar despite being perfused by adult serum and inflammatory cells in an adult environment. These data sugg est that the fetal fibroblast is the major effector cell far scarless fetal skin repair.