LAUSR

BACKGROUND Wound healing is a widespread health problem that imposes a financial burden on health systems. Cell therapy with genetically modified ADSCs is a promising strategy for dysregulated wound repair. E2F transcription factor 1 is a bidirectional regulator of cytokines. Here, we aimed to investigate the impact and potential mechanism of E2F1-/- ADSCs in promoting the wound healing process. METHODS Forty-five C57BL/6 mice (SPF, male) with 10 mm full-thickness wound were randomly treated with subcutaneous injection of 2 x 106 wild type (WT) ADSCs, 2 z 106 E2F1-/- ADSCs or PBS. The wound closure rate was monitored at day 0, 3, 7, 10, and 14 post-treatment. The collagen synthesis, angiogenesis, and wound contraction were calculated by Masson, IHC and IF staining (CD31, KI67), WB (α-SMA, collagen I, VEGF, and TGF-β1) separately at day 14. In vitro, the conditioned media (CM) of WT ADSCs and E2F1-/- ADSCs were collected to evaluate the impact on proliferation, migration, and angiogenesis. RESULTS In vivo, the E2F1-/- ADSCs group exhibited increased healing rate, proliferating vessels, and collagen synthesis compared to control at day 14 (P <0.05). Moreover, E2F1-/- ADSCs showed enhanced VEGF and TGF-β1 expression in the wound site and CM, and the CM from E2F1-/- ADSCs promoted the proliferation, migration, and tube formation of co-cultured cells in vitro (P < 0.05). CONCLUSIONS The E2F1-/- ADSCs exhibited a strong paracrine ability to improve the vascularization process and collagen deposition, thereby accelerating the wound healing in the rodent model.