Therapeutic efficacy and safety of mesenchymal stem cells-derived exosomes in the treatment of radiation enterocolitis
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Abstract:
Objective: To explore the effects of mesenchymal stem cell-derived exosomes (MSC-Exo) on the in vitro proliferation and migration of human colorectal cancer cells (CT26), and assess the effects and safety of MSC-Exo treatment for tumor-bearing mouse model with radiation enteritis (RE). Methods: Commercially available liquid dressing products containing MSC-Exo (MSC-Exo product) were utilized for this study. Exosome components were identified through Nanoparticle Tracking Analysis (NTA), transmission electron microscopy (TEM), and WB analysis. The effects of MSC-Exo product on CT26 cell proliferation and migration were detected using the CCK-8 and Transwell assays. A CT26 tumor-bearing mouse model was established, and the mice were intragastrically administered with 400 μL MSC-Exo product, MSC culture medium, or saline for 7 consecutive days to evaluate the effects of MSC-Exo product on tumor growth and mouse survival in vivo. A radiation enteritis tumor-bearing mouse model was also established, and administered similar treatments. The efficacy and safety of MSC-Exo product treatment for RE were evaluated through H-E staining of small intestine tissues. Results: NTA, TEM, and WB analyses confirmed the presence of MSC-Exo in the commercial liquid dressing products. In vitro studies showed that MSC-Exo product did not promote tumor proliferation or migration. In vitro studies revealed that MSC-Exo product did not promote the proliferation and migration of colon cancer CT26 cells and was thus safe. In vivo studies revealed that gavage administration of MSC-Exo product did not affect tumor growth and the survival period of tumor-bearing mice. However, after treating radiation enteritis tumor-bearing mouse model with MSC-Exo product via gavage, the symptoms of bloody and mucous stool were relieved. H-E staining results demonstrated improved tissue morphology integrity in the intestinal tissues of the mice compared with that of the mice in the control group, suggesting that MSC-Exo product was effective in treating RE in tumor-bearing mice and was safe in terms of oncogenicity and tumor metastasis. Conclusion: Commercial liquid dressing products containing MSC-Exo do not promote the proliferation and migration of colon cancer cells in vitro, and have no obvious effects on tumor growth and survival period of CT26 cell tumor-bearing mice, but are effective in treating RE in the tumor-bearing mouse model and improve intestinal tissue damage.