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Metformin is commonly prescribed as a hypoglycemic agent following the onset of type 2 diabetes mellitus. This study aimed to investigate pro- and/or anti-angiogenic effects of Metformin on human bone marrow mesenchymal stem cells. Cells were incubated with different doses of Metformin including 0.5, 1, 10, 50, 100, 200 and 500 μM for 14 days. Cell viability and total fatty acids profile were examined by MTT and gas chromatography methods. Differentiation of cells to endothelial lineage was studied by monitoring the expression of VEGFR-2 and Tie-2 receptors and VE-cadherin via real-time PCR and western blotting. Angiogenic potential and migration of cells were assessed by tubulogenesis and Transwell migration assays. PCR array was performed to analyze mTOR signaling. CD133+ and VEGFR-2+ cells were detected in blood samples of non-diabetic control, diabetic subjects and diabetics received Metformin. Metformin dose-dependently reduced cell survival. Decreased content of palmitate and oleate coincided increased level of stearate, palmitoleate, and linoleate (p 0.05). These data support a notion that Metformin could blunt the angiogenic behavior of human mesenchymal stem cells by modulating mTOR signaling pathway.
Montazersaheb et al. (Thu,) studied this question.