Therapeutic Effect of Exosomes Derived From Bone Marrow Mesenchymal Stem Cells on Lingual Papillae Mucositis Induced by ۵-fluorouracil in Albino Rats

Introduction: ۵-fluorouracil (۵-FU) is one of the prevalent anti-cancer drugs that is commonly used in chemotherapeutic modalities to treat head and neck solid cancers. However, various studies have reported that ۵-FU has the ability to generate toxicity in different tissues, causing oral mucositis. Using exosomes derived from stem cells is gaining huge attention for therapies, as it may have certain advantages over adult stem cell-based therapies. This study aimed to evaluate the therapeutic effect of bone marrow-derived stem cells exosomes on the cytotoxicity induced by ۵-FU on the lingual papillae of albino rats. Materials & Methods: Thirty male albino rats weighing between ۱۵۰-۲۰۰ grams were equally and randomly divided into ۳ groups as follows: Group I (control group): containing ۱۰ rats, received saline daily via oral gavage for ۱۴ days. Group II (۵-FU group): containing ۱۰ rats, received a single intraperitoneal (IP) injection of ۵-FU® drug (۵۰ mg/kg) each. Group III (۵-FU + exosomes group): containing ۱۰ rats; the rats was treated as group II, then received a single injection of exosomes through the tail vein day ۲ (۱۰۰ μg/kg/dose suspended in ۰.۲ mL PBS). Rats of each group were euthanized after ۱۴ days, and tongue specimens were collected for histological, ultrastructural, and immunohistochemical evaluation. Results: In the ۵-FU treated group, there were marked degenerative changes of the filiform papillae, such as areas of keratin separation and hyperkeratinization and the fungiform papillae showed atrophy and deformed taste buds. The exosomes-treated group, however, showed marked improvement in histological, ultrastructural, and immunohistochemical findings. Conclusion: Exosomes derived from bone marrow mesenchymal stem cells (MSCs) exerted an obvious therapeutic effect against the induced mucositis caused by the cytotoxic effect of ۵-FU, as reflected in improved histological, ultrastructural, and immunohistochemical findings.

کلیدواژه ها:

۵-Fluorouracil ، Bax ، Exosomes ، Mesenchymal Stem Cells derived Exosomes ، Oral Mucositis (OM)