Metformin Weakens the Angiogenic Potential of Human Bone Marrow Mesenchymal Stem Cells (hBMSCs) by Activating Mammalian Target of Rapamycin (mTOR) Signaling

Abstract

To study metformin’s effect on the angiogenesis of human bone marrow mesenchymal stem cells (hBMSCs). Cells were treated with metformin (0.5, 1, 10, 50, 100, 200 and 500 βM) for 14 days, followed by analysis of cell viability and total fatty acid profile, level of VEGFR-2, Tie-2, VE-Cadherin and mTOR signaling protein, cell differentiation by microtubule generation and cell migration by transwell assay. Metformin dose dependently decreased cell survival and reduced palmitate, oleate, stearate and linoleate content. In addition, it downregulated VEGFR-2 and Tie-2 and decreased the angiogenic potential of BMSCs and down-regulated VE-Cadherin. Western blot and PCR analysis showed that metformin activated mTOR signaling and up-regulated the transcription of autophagyrelated genes. Metformin can reduce BMSCs angiogenic potential by regulating mTOR signal pathway.