Local multiple-site injection of MnSOD-modified hUCMSCs alleviates combined radiation and wound injury in mice

Background Combined radiation and wound injury is a refractory complication in radiotherapy, closely associated with persistent radiation-induced oxidative stress and apoptosis. Mesenchymal stromal cell (MSC) therapy shows promise but is limited by poor cell survival in the irradiated microenvironment. This study investigated the therapeutic effects and mechanisms of local injection of human umbilical cord mesenchymal stromal cells genetically modified to overexpress manganese superoxide dismutase (MnSOD-hUCMSCs) on combined radiation and wound injury. Methods MnSOD-hUCMSCs were established using an adenoviral vector, and their conditioned medium (MnSOD-CM) was collected. A mouse model of combined radiation and wound injury was used to evaluate the wound-healing effects of local MnSOD-hUCMSCs injection. In vitro , MnSOD-CM was applied to irradiated HaCaT and HFF-1 cells. Cell viability, migration, oxidative stress, mitochondrial function, and apoptosis were assessed. Results MnSOD-hUCMSCs with improved antioxidant capacity were generated, and their conditioned medium (MnSOD-CM) recapitulated the cytoprotective effects of MnSOD-hUCMSCs in vitro . Local injection of MnSOD-hUCMSCs significantly promoted wound healing, accelerated re-epithelialization, increased collagen deposition, and reduced apoptosis in vivo . Mechanistically, MnSOD-hUCMSCs exerted effects through paracrine-mediated delivery via their conditioned medium, regulating the Bax/Bcl-2 balance and inhibiting PARP cleavage to block apoptosis. Conclusion Local injection of MnSOD-hUCMSCs effectively treats combined radiation and wound injury via their paracrine factors present in the conditioned medium. These findings suggest that paracrine factors secreted by MnSOD-hUCMSCs play a critical role in alleviating radiation-induced skin injury. The relative contribution of paracrine factors and other potential mechanisms warrants further investigation. This study offers a novel therapeutic strategy for radiation-induced skin injury.