Wound healing of human skin transplanted onto the nude mouse after a superficial excisional injury: human dermal reconstruction is achieved in several steps by two different fibroblast subpopulations

It has been established that human skin grafted onto the nude mouse is able to regenerate after being subjected to a full-thickness wound. In the pres ent work, we sought to determine the cells involved in the connective tissu e repair process following superficial wounding, Two months after transplan tation, superficial wounds were made at the center of the graft using mecha nical dermabrasion, At various times thereafter, ranging from 2 days to 6 w eeks, healing grafts were harvested and processed for immunohistological st udy with species-specific and cross-reacting antibodies directed against hu man or mouse antigens, The grafted human skin regenerated according to the following series of events. First, the human dermis underneath the scab bec ame devoid of human fibroblasts while the surrounding human dermis preserve d its own characteristics. The TUNEL reaction on early-phase healing wounds indicated that apoptosis occurred steadily within this area and could be t he mechanism by which cells disappeared. Moreover, cell death was reduced w hen the wound was covered,vith an occlusive dressing. The human dermis bene ath the wound was then invaded by mouse cells which deposited type I collag en on the human extracellular matrix and produced mouse granulation tissue at the surface above it. Human keratinocytes migrated over the mouse granul ation tissue to reconstruct the epidermis, Eventually, the mouse granulatio n tissue was progressively invaded by human fibroblasts, which formed a hum an neodermis, The overall process appeared to depend upon several successiv e epithelial-mesenchymal interactions, which were not species-specific. Thi s suggests that myofibroblasts arise from a specific subpopulation of fibro blasts, probably located at the interface between the dermis and adipose ti ssue, and that the granulation tissue is eventually remodeled by another po pulation of fibroblasts present in the human dermis.