Potential Role of Metformin in Mesenchymal Stem Cell-based Osteogenic and Angiogenic Coupling

Abstract

Objective: Metformin is a first-line medication used to treat type 2 diabetes. Non-antidiabetic effects of metformin have recently included its osteogenic effect on bone marrow mesenchymal stem cells (BMSCs). The purpose of the present work was to study the potential effects of metformin in the osteogenic/angiogenic coupling. Results: Clinically relevant doses of metformin exerted both direct and indirect effects on endothelial cells capillary tube formation, a well-known assay used to analyze angiogenic effects in vitro. Also, metformin directly induced BMSCs to express and secrete vascular endothelial growth factor (VEGF). Metformin induced these responses in both BMSCs and endothelial cells due to the fact that they express functional organic cation transporters (OCTs), critical cellular determinants of metformin intracellular uptake and activity. This study provides preliminary data and further research is required to gain a better understanding on the role of metformin as a potential osteogenic/angiogenic factor in skeletal regeneration.