Abstract:ObjectiveTo investigater the therapeutic effects of mouse adipose-derived mesenchymal stem cells(mADSCs) on chemotherapy-induced oral mucositis(CIOM), along with their potential mechanisms. MethodsA mouse CIOM model was established by intraperitoneally injecting 5-fluorouracil(5-FU) and chemically damaging the tongue mucosa with 70% acetic acid, followed by the injection of mADSCs into the ulcerated area. Hematoxylin and eosin(H-E) staining was performed to observe histological changes, while qRT-PCR was used to measure the expression of inflammatory cytokines and oxidative stress-related factors. Immunohistochemical staining assessed the expression of oxidative stress-related proteins. ResultsAfter local injection of mADSCs, the ulcer area in the experimental group was reduced compared to the control group on the ninth day of the experiment., along with restoration of the epithelial structure, decreased inflammatory cell infiltration, and lowered expression of interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), indicating therapeutic effects on CIOM. Additionally, treatment with mADSCs resulted in elevated expression of oxidative stress-related factors heme oxygenase 1(HO-1), superoxide dismutase 1(SOD-1), and Nuclear factor(erythroid-derived 2) -like 2(NFE2L2)(Nrf2) in the lesions, while Kelch-like ECH-associated protein 1(Keap1) expression decreased, indicating that these therapies may alleviate oxidative stress through the Nrf2/Keap1 signaling pathway in the treatment of CIOM. ConclusionThis study provides preliminary insights into the roles and mechanisms of mADSCs in treating chemotherapy-induced oral mucositis, offering a theoretical foundation for new treatment strategies for CIOM.