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The Protective Effects of MSC‐Derived Exosomes Against Chemotherapy‐Induced Parotid Gland Cytotoxicity

Year: 2025
Type: article
Abstract: Background: Fluorouracil (5‐FU) is one of the most popular chemotherapeutic agents used in various cancer therapy protocols. Cell‐free therapy utilizing exosomes is gaining increased popularity as a safer option due to concerns over potential tumor progression following stem cell therapy. Methods: Parotid glands of albino were treated with a single bone marrow mesenchymal stem cell (BMMSC)‐derived exosomes injection (100 μg/kg/dose suspended in 0.2 mL phosphate‐buffered saline [PBS]), a single 5‐Fu injection (20 mg/kg), and BMMSC‐derived exosomes plus 5‐FU and compared to control group (daily saline injections). After 30 days, the parotid glands were examined using qualitative histological evaluation, immunohistochemical evaluation using rabbit polyclonal mouse antibody to Ki‐67, caspase 3, and iNOS , as well as quantitative real‐time polymerase chain reaction (RT‐PCR) to evaluate gene expression of TGFβ1 , TNF-α , and BCL-2 . Results: Histological examination of the parotid gland revealed that BMMSC‐derived exosomes restored the glands’ architecture and repaired most of the distortion created by 5‐FU. Immunohistochemical expression of tumor proliferation and cell death markers were restored to normal levels in the exosome‐treated groups that were similar to the control group. Furthermore, BMMSC‐derived exosomes reversed the effects of 5‐FU on quantitative gene expression levels and showed a significant decrease in TNF-α ( p < 0.001) and a significant increase in TGFβ ( p < 0.0001) and BCL-2 ( p < 0.05) when compared to 5‐FU treatment. Conclusion: Within the limitations of the current study, BMMSC‐derived exosomes have the potential to counteract the cytotoxic effects of 5‐FU on the parotid glands of rats in vivo. Further studies are deemed necessary to simulate clinical scenarios.
Language: English
Open Access status: gold
Estimated APC paid: $1,560
OpenAlex ID: W4409149828
FWCI: 0.522
Cites: 112
Cited by: 2
Related to: 10