DMBT1 in Adipose-Derived Stem Cell-Derived Exosomes Participates in Alleviating Ferroptosis to Promote Diabetic Wound Healing.

Diabetic wounds represent one of the most severe complications of diabetes, and their clinical management remains challenging. This study investigated the therapeutic potential of adipose-derived stem cell-derived exosomes (ADSCs-Exo) for diabetic wounds. We isolated ADSCs and their exosomes, and by using Transwell and CCK-8 assays, we found that ADSCs-Exo were associated with proliferation and migration of keratinocytes and fibroblasts, and that they also enhanced the angiogenic activity of endothelial cells in vitro. In contrast, these promotive effects were significantly attenuated when exosomes derived from ADSCs with DMBT1 knockdown via siRNA (ADSCssiDMBT1-Exo) were applied. In a diabetic mouse model, ADSCs-Exo treatment significantly accelerated wound healing, whereas the pro-healing capacity of ADSCssiDMBT1-Exo was markedly reduced. To further explore the underlying mechanism, we performed RNA sequencing, which suggested that ADSCs-Exo might exert their therapeutic effects by alleviating ferroptosis and promoting cell proliferation. Subsequent experiments, including TEM, ROS assays, JC-1 staining, and tissue immunofluorescence, provided further support for these mechanistic findings. In summary, this study demonstrates that DMBT1 in ADSCs-Exo participates in alleviating ferroptosis in diabetic wound tissue, which may contribute to creating a favorable microenvironment for cell proliferation and promoting wound healing. This discovery provides a novel potential therapeutic target and strategy for the clinical treatment of diabetic wounds.