The Effects Of Adipose-Derived Stem Cells On Skin Grafts

ObjectiveThe aim of this study was to evaluate the effects of ASCs on skin grafts through promoting angiogenesis, decreasing inflammatory response as well as modifying the accumulation of different collagen types at different time points.MethodsASCs were isolated, cultured, and injected under skin grafts in 15 rats (ASC group). An additional 15 rats served as controls (PBS group). Each group was divided equally into five subgroups of three rats each according to the time of euthanasia, that is,1,2,3,7, or 14 days after the operation. The graft survival rates and blood flow were assessed with laser Doppler blood flowmetry (LDF). Angiogenesis was assessed with vascular endothelial growth factor (VEGF) immunohistochemistry, and vWF immunofluorescence was simultaneously performed to detect transplanted CM-Dil-labeled ASCs at day 14. Collagen frameworks were assessed with Masson's trichrome staining and picrosirius red staining. Additionally, the immunohistochemical staining intensities for transforming growth factor beta 3 (TGF-?3) were assessed. The expression of inflammation-related cytokines was detected with real-time RT-PCR, and the distributions of the macrophage subtypes were measured with immunofluorescence and western blot.ResultsWe found that the skin graft blood perfusion was significantly increased in the ASC group. The neovascularization, collagen deposition, collagen type I to type III ratio and levels of VEGF and TGF(33 in the ASC group were markedly higher than those in the PBS group at day 14. Additionally, in the ASC group, the quantity of infiltrated inflammatory cells and the levels of iNOS, IL-1?,and TNF-a were remarkably decreased, whereas the levels of IL-10 and Arg-1 were substantially increased.ConclusionsOur findings suggest that autologous ASC transplantation can effectively improve skin-graft blood perfusion and survival condition by promoting angiogenesis, decreasing inflammatory response as well as modifying the accumulation of different collagen types at different time points. Additionally, the anti-inflammatory role of ASCs may indirectly contribute to skin-graft survival via its effect on macrophage polarization.