Knocking out Smad3 favors allogeneic mouse fetal skin development in adult wounds

Abstract

Fetal skin development represents a process of the interaction between skin progenitor cells and their unique extracellular matrix niche, which is also important for the mechanism study of skin progenitor cell differentiation and fetal scarless wound healing. Thus, a change in the niche environment, such as altered expression levels of growth factors or cytokines, may also change the outcome of fetal skin development. This study tested the hypothesis that deletion of mouse Smad3 creates a favorable environment for fetal skin development in adult wounds. Fetal skin of green fluorescent protein mouse (C57BL/B6) of gestational day 16.5 was respectively transplanted to the wound beds of wild-type (WT), heterozygous (HT), and homologous (KO) Smad3 deletion mice (C57BL/B6 × 129SV). The results showed that green fluorescent protein fetal mouse skin after its transplantation developed much better into hair follicle containing skin in KO or HT wound beds than in WT wound beds with significant differences in the number of follicles per mm(2) among the three groups at 1, 2, and 3 weeks posttransplantation (p < 0.05). In addition, less fibrosis was observed in KO wounds than in HT and WT wounds with significant difference in the wound bed thickness among the three groups at 3 weeks posttransplantation (p < 0.05). Interestingly, there was a delayed graft rejection in the KO group when compared with the HT and WT groups. In conclusion, deletion of Smad3 in a wound bed creates a better environment for skin progenitor cell differentiation and fetal skin development. Translation of such a concept to the creation of a wound environment that is favorable for adult stem cell differentiation and skin appendage formation may become an important strategy for the regeneration of wounded skin.