Synergistic Effects of TNF-α and VEGF on mESC-Derived Endothelial Progenitor Cells in Promoting Wound Healing
Skin wound healing is one of the major clinical problems worldwide.Angiogenesis and the in-flammation response are critical processes that influence wound healing and tissue regeneration.Endothe-lial progenitor cells(EPCs)play a pivotal role in vascular endothelial repair and the recruitment of in-flammatory cells to promote wound healing.However,direct in vivo delivery of EPC is inefficient and can impair cell viability and function,thereby affecting therapeutic efficacy.Therefore,it is necessary to im-prove the biological functions of EPC to promote wound healing.This study induced the generation of CD133+CD34+EPC from mouse embryonic stem cells(mESCs)under the influence of 10 ng/mL Vascu-lar Endothelial Growth Factor(VEGF)and 5 ng/mL basic Fibroblast Growth Factor(bFGF).We used mESC-derived EPC as the research object,and applied exogenous tumor necrosis factor-α(TNF-α)and Vascular Endothelial Growth Factor(VEGF)to mESC-EPC.The results showed that the co-treatment with 10 ng/mL TNF-α and 10 ng/mL VEGF significantly promoted the adhesion,cell migration,and lu-minal formation abilities of EPC compared to the single-factor treatment(P＜0.01).Further,using a murine full-thickness skin wound model,local administration of 10 ng/mL TNF-α and 10 ng/mL VEGF in conjunction with EPC treatment markedly accelerated wound closure(P＜0.05),thickened the der-mal layer of the regenerated skin(P＜0.001),and promoted the maturation of the capillary network formed by CD31+endothelial cells mediated by angiopoietin ANG1 and ANG2.As wound healing pro-gressed,the expression of the pro-inflammatory factor TNF-α was down-regulated(13 days after surgery,the relative expression levels of TNF-α in PBS group,EPC group,VE group,TE group and VTE group were 0.73±0.01,0.60±0.02,0.42±0.02,0.36±0.01,0.34±0.03,respectively),creating a conducive inflammatory microenvironment for wound healing.In summary,the synergistic effects of 10 ng/mL TNF-α and 10 ng/mL VEGF enhance the biological functions of EPC,as well as accelerate wound closure and tissue remodeling in mouse skins by promoting new angiogenesis and early inflammato-ry responses.This offers new insights into celluiar intervions for wound healing therapies.
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