ANTI-INFLAMMATORY AND ANTI-APOPTOTIC THERAPEUTIC EFFECTS OF MESENCHYMAL STEM CELLS-DERIVED EXOSOMES ON THE PANCREAS OF STREPTOZOTOCIN-DIABETIC RATS

The rising prevalence and serious complications of type 1 diabetes mellitus (T1DM)have made it a huge challenge that significantly jeopardizes public health, with high morbidity resulting in poor quality of life.The safety and therapeutic excellence of cell-free exosomes(EXs) derived from mesenchymal stem cells (MSCs) over MSCs transplantation suggested a novel perspective for DM and the treatment of its complications. The current design wasconducted toinvestigate the therapeutic potentialities of management in rats. For 4 consecutive weeks, 4rat groups were conducted as control, EXs, STZ-diabetic (D), and D+EXs groups. The results showed that the untreated diabetic rats exhibited marked hyperglycemia evidenced by elevated serum glucose and HbA1c levels and declined insulin and C-peptide levels compared to control rats. In addition, pancreatic tissues of the untreated diabetic rats revealed significant progression in oxidative stress (↑ MDA, H₂O₂, and NO), inflammation (↑ IL-6, TGF-β, and TNF-α), and apoptotic statuses (↑annexin V, P53, caspase-3, and ↓Bcl-2) regarding control. However, all results reverted near to normal levels following intravenous injection of diabetic rats with a single dose of MSCs-EXs (500 µg/mL) compared to the untreated diabetics. These results were confirmed by the enhanced histological picture of diabetic rats pancreas, concerning the diabetic-untreated rats.The biochemical and flow cytometric assessments evidenced that diabetic rats treated with marked pancreatic regenerative anti-inflammatory, immunomodulation, antioxidant, and anti-apoptotic potentialities in counteracting the induced hyperglycemia.