Abstract

Skin is the largest organ of the human body. Skin wound is one of the most common forms of wound. Mesenchymal stromal cells (MSCs) have been used to aid skin wound healing via their paracrine factors. Because the secretome of MSCs can be greatly enriched and amplified by treatment with IFN-γ and TNF-α (IT), we here tested whether supernatant derived from MSCs pretreated with IT, designated as S-MSCs-IT, possesses improved wound healing effect by using a murine model of cutaneous excision, S-MSCs-IT was found to be more potent in promoting angiogenesis, constricting collagen deposition and accelerating wound closure than control supernatant (S-MSCs) during the healing of skin wound. VEGFC, but not VEGFA, was greatly upregulated by IT and was found to be a key factor in mediating the improved wound healing effect of S-MSCs-IT. Our results indicate that the beneficial paracrine effect of MSCs on wound healing can be enhanced by pretreatment with inflammatory cytokines. IT treatment may represent a new strategy for optimizing the therapeutic effect of MSCs on skin injuries.Significance statementMesenchymal stromal cells (MSCs) have been demonstrated to accelerate wound healing; however, MSCs or MSC-conditioned medium did not exhibit superior effect in all cases, indicating that the beneficial effect of MSCs on wound healing needs to be further improved. The results of this study indicate that the beneficial paracrine effect of MSCs on wound healing can be enhanced by pretreatment with inflammatory cytokines. TNF-α and IFN-γ treatment may represent a new strategy for optimizing the therapeutic effect of MSCs on skin injuries.