Prolonged incubation with Metformin decreased angiogenic potential in human bone marrow mesenchymal stem cells

Prolonged incubation with Metformin decreased angiogenic potential in human bone marrow mesenchymal stem cells


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نویسندگان: سهیلا منتظرصاحب , علیرضا نورآذریان , رضا رهبرقاضی , حجت اله نوزاد چروده

کلمات کلیدی: Human mesenchymal stem cells; Metformin; Angiogenic potential; mTOR Signaling

نشریه: 4741 , 2018 , 108 , 2018

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نویسنده ثبت کننده مقاله رضا رهبرقاضی
مرحله جاری مقاله تایید نهایی
دانشکده/مرکز مربوطه مرکز سلولهای بنیادی
کد مقاله 64060
عنوان فارسی مقاله Prolonged incubation with Metformin decreased angiogenic potential in human bone marrow mesenchymal stem cells
عنوان لاتین مقاله Prolonged incubation with Metformin decreased angiogenic potential in human bone marrow mesenchymal stem cells
ناشر 7
آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ بلی
عنوان نشریه (خارج از لیست فوق)
نوع مقاله Original Article
نحوه ایندکس شدن مقاله ایندکس شده سطح یک – ISI - Web of Science
آدرس لینک مقاله/ همایش در شبکه اینترنت

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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). Metformin decreased the angiogenic potential of cells by decreasing VEGFR-2 and Tie-2 expression (p < 0.05). The protein level of VE-cadherin decreased in cells received Metformin. Compared to the control, Metformin blunted the expression of VEGF subtypes and directed cells to energy status by induction of PRKAA1, PRKAB2, and PRKAG1 genes (p < 0.05). Non-significant differences were observed regarding the number of CD133 and VEGFR-2 cells in blood samples (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.

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نویسنده نفر چندم مقاله
سهیلا منتظرصاحباول
علیرضا نورآذریانچهارم
رضا رهبرقاضیششم
حجت اله نوزاد چرودههفتم

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