Functional and histological evaluation of bone marrow stem cell-derived exosomes therapy on the submandibular salivary gland of diabetic Albino rats through TGFß/ Smad3 signaling pathway.

BACKGROUND: To prevail over diabetes mellitus and its numerous complications, researchers are seeking new therapies. Exosomes are natural cargo of functional proteins and can be used as a therapeutic delivery of these molecules. OBJECTIVE: The aim of this study was to evaluate the effect of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) as a therapeutic intervention in salivary gland diabetic complications. METHODS: Ten adult healthy male Albino rats, weighing about 150-200 g were grouped into 2 groups. Diabetic group I: consisted of 5 streptozotocin (STZ)-induced diabetic rats. Exosomes treated group II: consisted of 5 STZ-induced diabetic rats, each animal received a single injection of exosomes (100 µg/kg/dose suspended in 0.2 ml PBS) through the tail vein. All animals were sacrificed after 5 weeks from the beginning of the experiment. Submandibular salivary gland samples were excised and processed for histological, ultrastructural examination and PCR for TGFß, Smad2 and Smad3. Blood glucose level was monitored weekly, salivary IgA and serum amylase were evaluated before and after diabetes induction and at the end of the experiment. RESULTS: Histological and ultrastructural results of the exosomes treated group were promising regarding the glandular and ductal elements with less fibrosis observed. Results of PCR supported the role of exosomes to inhibit the diabetic sequalae in salivary gland and its complications through inhibiting TGFß and its related pathway via Smad2 and Smad3. Blood glucose levels were reduced. In addition, salivary glands' function was improved as evidenced by reduction in serum amylase and salivary IgA. CONCLUSION: BM-MSC-derived exosomes could be a novel therapeutic strategy for diabetic complications involving salivary glands.