d-Tocotrienol preconditioning improves the capability of bone marrow-derived mesenchymal stem cells in promoting wound healing by inhibiting BACH1-related ferroptosis

Wound healing is a complex physiological process for maintaining skin integrity after a wound. Bone marrow-derived mesenchymal stem cells (BMSCs) are excellent cellular candidates for wound healing, which could be enhanced by exogenous stimulation. We aimed to explore the role of & delta;-Tocotrienol (& delta;-TT) in BMSC ability of wound healing. Firstly, transcriptome and single-cell analysis were used to explore the genes and pathways related to ferroptosis in wound tissues. In vitro, cell proliferation, migration, and angiogenesis of & delta;-TT-BMSCs were detected. In addition, qRT-PCR and immunofluorescence (IF) were applied for observing the promoting wound healing ability of & delta;-TT-BMSC conditioned medium (CM) on NIH-3T3 and PAM-212 cells. The level of ferroptosis was determined by the mitochondrial membrane potential and total/lipid reactive oxygen species (ROS) in the cells and the morphological changes of mitochondria were observed by transmission electron microscope. The BTB and CNC homology 1 (BACH1) expression and activation of the PI3K/AKT signaling pathway were detected by IF and western blot (WB). The effect of & delta;-TT-BMSCs on wound healing was observed in vivo. The regulatory mechanism of & delta;-TT-BMSCs on ferroptosis was verified by IHC and IF staining. In vitro, & delta;-TT-BMSCs declined the level of lipid ROS in NIH-3T3 and PAM-212 cells and enhanced mitochondrial membrane potential. In vivo, & delta;-TT-BMSCs promoted wound healing in mice by decreasing ferroptosis. In terms of mechanism, & delta;-TT-BMSCs inhibited the expression of BACH1 and activated PI3K/AKT signaling pathway. This study demonstrated the ability of & delta;-TT-BMSCs to promote wound healing by inhibiting BACH1-related ferroptosis. In addition, PI3K/AKT signaling pathway was activated by & delta;-TT-BMSCs and could be involved in wound healing. & delta;-TT-BMSCs might be a promising strategy for treating wounds.

Automated summary

This study found that δ-tocotrienol (δ-TT) can enhance the wound healing ability of bone marrow-derived mesenchymal stem cells (BMSCs). Through in vitro and in vivo experiments, it was found that δ-TT-BMSCs can inhibit the progression of ferroptosis and promote wound healing. This study provides a new strategy for treating wounds.