Specific disruption of Lnk in murine endothelial progenitor cells promotes dermal wound healing via enhanced vasculogenesis, activation of myofibroblasts, and suppression of inflammatory cell recruitment

BackgroundAlthough endothelial progenitor cells (EPCs) contribute to wound repair by promoting neovascularization, the mechanism of EPC-mediated wound healing remains poorly understood due to the lack of pivotal molecular targets of dermal wound repair.Methods and ResultsWe found that genetic targeting of theLnkgene in EPCs dramatically enhances the vasculogenic potential including cell proliferation, migration, and tubule-like formation as well as accelerates in vivo wound healing, with a reduction in fibrotic tissue and improved neovascularization via significant suppression of inflammatory cell recruitment. When injected into wound sites,Lnk-/-EPCs gave rise to a significant number of new vessels, with remarkably increased survival of transplanted cells and decreased recruitment of cytotoxic T cells, macrophages, and neutrophils, but caused activation of fibroblasts in the wound-remodeling phase. Notably, in a mouse model of type I diabetes, transplantedLnk-/-EPCs induced significantly better wound healing thanLnk+/+EPCs did.ConclusionsThe specific targeting of Lnk may be a promising EPC-based therapeutic strategy for dermal wound healing via improvement of neovascularization but inhibition of excessive inflammation as well as activation of myofibroblasts during dermal tissue remodeling.