Melatonin improves the therapeutic role of mesenchymal stem cells in diabetic rats.

The present study aimed to investigate the role of bone marrow mesenchymal stem cells (MSCs) and/or melatonin (MT) for improvement of β-cell functions in STZ diabetic rats. Male albino rats (130-150 g) were divided into six groups. CONTROL GROUP: received phosphate-buffered saline (PBS); melatonin group received melatonin (10 mg/kg b.wt./day for 2 months by oral gavage); diabetic untreated group; diabetic group treated with melatonin; diabetic group treated with MSCs (a single intravenous injection of 3 × 106 cell in PBS); and diabetic group co-treated with stem cells and melatonin. The results showed significant improvement in glucose, insulin, total antioxidant, and malondialdehyde level in diabetic rats treated with either MSCs alone or in combination with melatonin. The imumuno-histochemical analysis showed that MSCs and/or melatonin treatment reduced the rate of inflammation and apoptosis of the islet cells as well as increased the rate of pancreatic cell division. Such results were indicated by a significant improvement in the level of TNF-α, IL-10, PCNA, and caspase-3 to levels very close to the control. Co-treatment of MSCs and MT resulted in an improvement in the tissue of the pancreas and reduced number of damaged β-cells. It can be concluded that co-treatment of stem cells and melatonin has a significant role in restoring the structural and functional efficiency of β-cells in the pancreas more than stem cells alone. Such results may be due to the role of melatonin as an antioxidant in increasing the efficiency and vitality of stem cells.