TNF-α-Activated Adipose–Derived Stem Cells Improve the Angiogenesis of Full-Thickness Skin Grafts Through the TNF-α/NF-κB Signaling Pathway

The repair of skin and soft tissue defects has been a long-standing topic of interest in plastic surgery. Skin grafts and flaps are the most commonly used methods for such repair, but both have some disadvantages. If a high-quality skin flap transplantation outcome could be obtained through simple skin grafting, it would surely benefit a majority of patients. Transplantation of adipose-derived stem cells (ADSCs) into skin and soft tissue wounds is a promising “therapeutic angiogenesis” strategy in this context. In the present study, we used TNF-α to mobilize ADSCs for the tissue regenerative process. Then, we injected the TNF-α-activated ADSCs intradermally into the donor skin of full-thickness skin grafts (FTSGs). TNF-α may activate ADSCs through the TNF-α/NF-κB pathway and enhance the ability of ADSCs to signal the paracrine secretion of the angiogenic factor IL-8, ultimately promoting the angiogenesis of donor skin. The use of vasculature-rich donor skin for grafting presented in our study could accelerate skin graft anastomosis; shorten the nutrient deprivation time of the epidermis, hair follicles, and dermis; and thereby improve the survival of FTSGs. Overall, the findings of the present study demonstrate a possible mechanism through which TNF-α acts on ADSCs to improve their angiogenic capacity and provide a novel approach for the repair of skin and soft tissue wounds. Comparative gene expression profiling analysis of RNA-seq data for TNF-α-Activated Adipose–Derived Stem Cells（t-ADSCs) and ADSCs