Mesenchymal Stem Cells Promote Healing of Radiation-Induced Skin Injury by Enhancing Mitochondrial Function

Background Human umbilical cord mesenchymal stem cells (HUCMSCs) are attractive for tissue repair because of their broad availability, low immunogenicity, and limited ethical constraints. However, the mechanisms by which HUCMSCs mitigate radiation‑induced skin injury, particularly effects on fibroblast mitochondrial function and energy metabolism, remain incompletely defined. Methods We investigated the effects of HUCMSCs on irradiated fibroblasts in vitro and in a murine model of radiation‑induced skin injury. In vitro assays evaluated fibroblast proliferation, migration, mitochondrial membrane potential, cellular respiration, and ATP production, and assessed intercellular mitochondrial transfer. In vivo , local subcutaneous administration of HUCMSCs was applied to the radiation‑injured skin in male C57BL/6J mice; wound closure, inflammatory marker expression, oxidative stress, angiogenesis, and extracellular matrix deposition were evaluated. Results In vitro , HUCMSCs markedly enhanced proliferation and migration of irradiated fibroblasts and restored mitochondrial membrane potential, respiration, and ATP synthesis; intercellular mitochondrial transfer contributed to these effects. In the murine model, local HUCMSC treatment significantly accelerated wound closure, decreased expression of inflammatory markers, attenuated oxidative stress, and promoted angiogenesis and extracellular matrix deposition in injured skin. Conclusions HUCMSCs alleviate radiation‑induced skin damage by remodeling fibroblast mitochondrial function and restoring cellular energy metabolism. These findings provide experimental support for mitochondria‑targeted, cell‑based therapies as a potential strategy to prevent or treat radiotherapy‑associated skin toxicity.