Potential of stem cell-derived exosomes to regenerate ß islets through Pdx-1 dependent mechanism in a rat model of type 1 diabetes.

Type 1 diabetes, has been recognized as an autoimmune disease. Like other immunological conditions, regulation of immune response is a key strategy to control the autoimmunity in diabetic patients. Mesenchymal stem cells have been shown to have a distinct potential in modulating the immune reactions. However, treatment with stem cells is combined with concerns about safety issues. To overcome these concerns, in this study, we have utilized the regenerative potential of exosomes isolated from menstrual blood-derived mesenchymal stem cells to restore the ß-cell mass and insulin production in type 1 diabetes. Exosomes are nanovesicles containing various cargos involved in cellular communications. Streptozotocin was used to induce islet destruction and diabetes in male Wistar rats. Then, exosomes were intravenously injected into animals at different time points and in a single or repeated therapeutic doses. After about 6 weeks, animals were euthanized and the pancreas was analyzed for the presence of the regenerated ß islets as well as the insulin secretion. The non-fasting blood glucose and the serum insulin level were also monitored during the study. Our results represented that menstrual blood-derived mesenchymal stem cell-derived exosomes enhance the ß-cell mass and insulin production in the pancreas of diabetic animals that received repeated doses of exosomes. Immunohistochemistry analysis also confirmed the presence of insulin in the islets of treated animals. Further investigations proposed that exosomes induce the islet regeneration through pancreatic and duodenal homeobox 1 pathway. The exosome tracking also revealed the homing of injected exosomes to the pancreas.

The effects of aminoguanidine on hippocampal cytokines, amyloid beta, brain-derived neurotrophic factor, memory and oxidative stress status in chronically lipopolysaccharide-treated rats.

INTRODUCTION: In the present study, the effects of aminoguanidine (AMG) on hippocampal cytokines, amyloid beta (Aß), brain-derived neurotrophic factor, oxidative stress status and memory in chronically lipopolysaccharide (LPS) treated rats were investigated. METHODS: The rats were divided into five groups and were treated: (1) Control (Saline), (2) LPS (1 mg/kg), (3-5) LPS- AMG50, LPS-AMG100, and LPS-AMG150 (AMG 50, 100 and 150 mg/kg 30 min before LPS injection). The treatment started five weeks prior to the behavioral experiments and continued during the behavioral tests (LPS injection two hours before each behavioral evaluation). Finally, the tissue was removed for biochemical measurements. RESULTS: The escape latency in Morris water maze test and the latency to enter the dark compartment in passive avoidance test in LPS group were significantly greater than the control group (P < 0.001), while, in LPS-AMG 100 and LPS-AMG150 groups they were less than LPS group (P < 0.001). Malondialdehyde (MDA), NO metabolites of hippocampal and cortical tissues and interleukin-6 (IL-6), Aß and tumor necrosis factor-α (TNFα) concentration in the hippocampus of LPS group were higher than control group (P < 0.001-P < 0.05). However, in LPS-AMG 100 and LPS-AMG150 group they were lower than LPS group (P < 0.001-P < 0.05). The thiol content and the activities of catalase (CAT) and superoxide dismutase (SOD) in both cortical and hippocampal tissues of LPS group were reduced compared to the control group (P < 0.001-P < 0.05). These factors enhanced in LPS-AMG 100 and LPS-AMG150 groups compared to LPS (P < 0.001-P < 0.05). The hippocampal content of brain-derived neurotrophic factor (BDNF) in LPS group was significantly lower compared to the control group (P < 0.001). All treated groups had higher BDNF content in comparison to LPS group (P < 0.01-P < 0.001). CONCLUSION: The findings indicated that the protective effects of AMG against LPS-induced memory were accompanied by decreasing of inflammatory cytokines, Aß, oxidative stress and increasing of anti-inflammatory mediators and BDNF.