Metabolic boosting via mitochondrial transfer for enhanced cell-based wound healing therapy

Persistent oxidative and inflammatory stresses within the wound microenvironment severely impair the healing process, driving acute wounds into chronic states. Although cell therapy represents a promising approach to accelerate tissue repair, it faces translational hurdles due to the metabolic exhaustion and attenuated efficacy of transplanted cells within this harsh environment. In this context, we developed a metabolically boosted cell therapy using mitochondrial transfer. Our findings demonstrated that integrating exogenous mitochondria into dermal fibroblasts (DFs) enhances cellular bioenergetics, significantly elevating oxidative phosphorylation (OXPHOS) and adenosine triphosphate (ATP) production without triggering cytotoxicity or senescence. Notably, this metabolic enhancement yielded mitochondria-transferred DFs (mDFs) with superior migratory capacity and a robust regenerative and immunomodulatory secretome. In a murine full-thickness skin defect model, mDF administration facilitated wound closure through re-epithelialization and neovascularization. Collectively, our functional and mechanistic investigations of mitochondrial boosting suggest an effective therapeutic platform for modulating immune responses and promoting wound healing.