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

Abstract

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, STZdiabetic 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 downregulating 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.

Anti-inflammatory and antioxidant potential capacities of AD-MSCs and BM-MSCs in suppressing pancreatic β-cells auto-immunity and apoptosis in rats with T1DM induced model

“…It is also worth noting that some mechanism exploration provide the potential of AD-MSC clinical application (Shree and Bhonde, 2017;Xie et al, 2017). Similar results in diabetic subjects were reported by Chen et al (2020) regarding AD-MSCs (1 × 10 6 cells/rat) injection, and by El-Kholy et al (2018);El-Sawah et al (2020) regarding BM-MSCs (1 × 10 6 cell/rat) injection; compared to the diabetic untreated rats.…”