BM-MSCS IMMUNOMODULATORY, ANTI-INFLAMMATORY, ANTI-APOPTOTIC AND ANTIOXIDANT CAPACITY ROLES IN MODULATING THE ALTERED TISSUES OXIDATIVE STRESS STATUS IN STZ-DIABETIC RATS: IN COMPARISON TO THE STANDARD INSULIN TREATMENT

Purpose: The present study was designed to investigate the probable hypoglycemic, antioxidant, anti-inflammatory, immuno-modulatory as well as anti-apoptotic protective capacities of bone marrow derived mesenchymal stem cells (BM-MSCs) in comparison with the standard insulin treatment in diabetic rats. Methods: Animals were divided into four groups control group, STZ-diabetic group (D), D+Insulin group and D+BM-MSCs group and the study continued for four consecutive weeks. Results: Insulin as well as BM-MSCs administration significantly improved the hyperglycemic status resulting from diabetes induction as evidenced by lowered blood glucose, HbA1c and AGEs levels, while enhanced serum insulin, C-peptide and HO-1 levels, compared to the diabetic group. Regarding oxidative stress and antioxidants, both insulin or BM-MSCs injection significantly attenuate the oxidative stress status resulting from diabetes induction, as evidenced by down-regulating MDA, ROS and XO levels, accompanied by up-regulating the antioxidants markers content as GSH, SOD, CAT, GST, TAC and HO-1 in different body tissues (Pancreas, Liver, Kidney and Heart) compared to the diabetic group. Also, treatment of diabetic rats with insulin or BM-MSCs significantly ameliorated the inflammatory disorders as indicated via markedly decreased serum inflammatory markers such as CRP, TNF-α, TGF-β and CD 95 compared to the untreated diabetic rats. In addition, insulin or BM-MSCs therapy was found to suppress pancreatic auto-immunity resulting in an obvious pancreatic cells apoptosis arrest in diabetic rats which was confirmed by declined pancreatic CD4+, CD8+, annexin V, P53 and caspase-3 levels accompanied by Bcl-2 level elevation compared to the diabetic group. Comparing both treatments together, most of the measured parameters were reverted back to near normal levels after BM-MSCs treatment confirming its anti-diabetic potency, in addition to their tissue protective and regenerative capabilities. Conclusion: Current findings clearly point out the health benefits of BM-MSCs more than insulin therapy in ameliorating various metabolic disorders including diabetic complications owing to their marked antioxidant, anti-inflammatory, immunomodulatory and anti-apoptotic characteristics.