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
P. Rossio-pasquier et al., 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, ARCH DERM R, 291(11), 1999, pp. 591-599
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.