الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The present study was established to investigate the role of bone marrow mesenchymal stem cells (MSCs) and melatonin (MT), alone or in combination with each other for improvement of beta cell functions in STZ-induced diabetic rat model. Also, to evaluate the role of melatonin in increasing the efficacy of MSCs.
Fifty two male albino rats (130-150g) were divided into six groups:
Control group: received the solvent phosphate buffer saline PBS by a single i.p. injection.
Melatonin group: received melatonin (10 mg/kg b.wt./ day) for 2 months by oral intubation.
Diabetic untreated group (DM): diabetic rats remained untreated along the experimental period. Diabetes was induced by a single i.p. injection of 45mg/kg b.wt. of streptozotocin.
DM+MT: diabetic rats treated with melatonin (10 mg/kg b.wt./ day) .
DM+MSCs group: diabetic rats treated with a single intravenous injection of mesenchymal stem cells (3×106 cell in PBS).
DM+ MSCs+ MT group: diabetic rats treated with both stem cells and melatonin at the same manner and dosage as mentioned before.
After two months, rats were sacrificed. The present results recorded a significant decrease in body weight and pancreatic weight in both diabetic untreated group and the diabetic group treated with melatonin. Treatment of diabetic rats with MSCs alone or in combination with melatonin significantly increased body and pancreatic weights when compared to diabetic non- treated group. Marked elevation of blood glucose level and significant reduction of insulin level was observed in diabetic non treated rats and diabetic ones treated with melatonin. Also, oxidative stress was recorded in the same groups. It was detected by significant elevation of serum MDA level concomitant with significant reduction of serum TAC. Treatment of diabetic rats with MSCs alone or in combination with melatonin improved the levels of glucose, insulin, MDA and TAC to the values close to the control level.
Diabetic non- treated rats and those treated with melatonin showed marked inflammation as indicated by high immune reactive cells of islets of Langerhans for the tumor necrotic factor-α as well as low level of serum cytokine IL-10. The inflammation induced by diabetes was reduced under the effect of MSCs treatment either alone or in combination with melatonin. Diabetic non- treated rats showed less cell proliferation rate (low expression of the proliferation marker PCNA) and high apoptotic rats (increased activated caspase-3 expression). Such results were counteracted toward the normal levels in diabetic groups treated with either MSCs alone or MSCs with melatonin.
The histological examination of diabetic untreated rats showed malformation in the pancreatic tissues including small and shrunken islets of Langerhans and destruction of beta cells. The pancreas of diabetic groups treated with MSCs and/or melatonin showed reorganization of islets and partial restoration of β-cells.
It can be concluded that MSCs showed improvement in all studied parameters. The ameliorative effect was more pronounced in diabetic group treated with both MSCs and melatonin than diabetic group treated with MSCs alone. The antioxidant property of melatonin may increase the efficacy and vitality of MSCs