Mitochondrial Transplantation Increases Dermal Fibroblast Proliferation and Accelerates Acute Wound Closure

The detrimental effects of dysfunctional mitochondria on cells and tissues have been shown to improve by healthy mitochondria transplantation. However, the feasibility of intercellular mitochondrial transfer for wound healing remains uncertain. This study examined whether healthy mitochondria transplantation promoted the healing of acute wounds. Isolated mitochondria derived from primary cultured normal human dermal fibroblasts were administered to primary cells of the same lineage, with confirmed cell uptake. Wound closure rate in in vitro scratch wound healing assays increased in a dose-dependent manner and was attenuated by treatment with the mitochondrial function inhibitor antimycin A. Gene expression analysis revealed significant increases in the cell proliferation markers MKI67 and PCNA, although no consistent changes in migration-related genes were observed. Cell proliferation rate increased to a maximum average of 1.4-fold after isolated mitochondrial administration, which was attenuated by antimycin A treatment. To verify the in vivo effects of isolated mitochondrial transplantation, mitochondria were obtained from mouse livers, and wound closure rate was analysed using a mouse wound healing model. The number of days to wound closure was significantly shortened in a dose-dependent manner, and this gain was attenuated by antimycin A. Our findings demonstrate that mitochondrial transplantation accelerates acute wound closure and enhances fibroblast proliferative activity. The observed increase in cell proliferation may contribute, at least in part, to the beneficial effects of mitochondrial transplantation on wound healing. These findings provide insight into the therapeutic potential of mitochondrial transplantation as a novel strategy for wound repair.