Therapeutic Role of Bone Marrow Mesenchymal Stem Cell-Derived Exosomes in Methotrexate-Induced Submandibular Salivary...

Methotrexate is a widely used chemotherapeutic agent associated with significant cytotoxic side effects, including xerostomia and salivary gland dysfunction. Exosomes have recently emerged as prospective therapeutic agents owing to their capacity to transfer bioactive compounds, including nucleic acids, proteins, and lipids. Therefore, this study was conducted to evaluate the effect of systemic injection of bone marrow mesenchymal stem cell-derived exosomes on submandibular glands of rats receiving Methotrexate. In this study, 36 adult albino rats were randomly divided into three groups (n = 12): Group I received phosphate-buffered saline (PBS); Group II received intraperitoneal Methotrexate (40 mg/kg); and Group III received Methotrexate followed by intravenous injection of BMMSC-derived exosomes (100-μg/kg/dose suspended in 0.2-mL PBS) via the tail vein after 7 days. After 5 weeks, rats were sacrificed, and submandibular glands were dissected out and prepared for histological and immunohistochemical examination. Statistical analysis was performed on the outcomes. Histological evaluation showed that BMMSC-derived exosomes markedly restored the normal glandular architecture and repaired most of the distortion created by Methotrexate. Immunohistochemically, BCL-2 expression was significantly upregulated, whereas TNF-α expression was significantly downregulated in the treated group. Our results concluded that systemically administrated BMMSC-derived exosomes exhibit therapeutic potential against Methotrexate-induced cytotoxicity in the submandibular salivary glands.