Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem CellsIn Vitro, and Increases Bone DensityIn Vivo

Abstract

Due to its pleiotropic effects, the commonly used drug metformin has gained renewed interest among medical researchers. While metformin is mainly used for the treatment of diabetes, recent studies suggest that it may have further application in anticancer and antiaging therapies. In this study, we investigated the proliferative potential, accumulation of oxidative stress factors, and osteogenic and adipogenic differentiation potential of mouse adipose-derived stem cells (MuASCs) isolated from mice treated with metformin for 8 weeks. Moreover, we investigated the influence of metformin supplementation on mice bone density and bone element composition. The ASCs isolated from mice who were treated with metformin for 8 weeks showed highest proliferative potential, generated a robust net of cytoskeletal projections, had reduced expression of markers associated with cellular senescence, and decreased amount of reactive oxygen species in comparison to control group. Furthermore, we demonstrated that these cells possessed greatest osteogenic differentiation potential, while their adipogenic differentiation ability was reduced. We also demonstrated that metformin supplementation increases bone density in vivo. Our result stands as a valuable source of data regarding the in vivo influence of metformin on ASCs and bone density and supports a role for metformin in regenerative medicine.

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

“…Another piece of evidence for the interrelationship of adipose metabolism with aging is that metformin, a drug approved to treat diabetes, appears to target a number of pro-aging activities, as it suppresses adipocyte proinflammatory responses, decreases ROS levels as well as adipose DNA damage and improves the balance of brown/white adipose upon obesity [29][30][31]. At organismal level, retrospective observational studies associate metformin with increased human lifespan, fewer age-related diseases, improved cognitive function and decreased cancer incidence, which cannot be explained by lowering blood glucose levels alone [32].…”

Metformin alleviates aging-associated cellular senescence of human adipose stem cells and derived adipocytes

“…We checked whether metformin pre-treatment was able to rescue the altered adipogenesis potential of aged-donor ASCs. Although the cells were treated with metformin, adipogenesis was induced in the absence of the drug to bypass its anti-adipogenic impact (Marycz, Tomaszewski et al 2016, Chen, Wang et al 2018). We found that metformin restored the adipogenic capacity of aged-donor ASCs at P11 to the level observed in young-donor ASCs.…”

“…Previous studies have demonstrated that metformin significantly improved ASC proliferation and function, which were correlated with a higher mitochondrial membrane potential (Smieszek, Kornicka et al 2019). Metformin was shown to decrease ROS production by ASCs (Marycz, Tomaszewski et al 2016). Here, we showed that aged-donor ASCs expressed and activated AMPK to a lower extent than young-donor ASCs, and that this impairment could be reversed by metformin treatment.…”

Metformin enhances osteogenic differentiation of stem cells from human exfoliated deciduous teeth through AMPK pathway

“…which express in hematopoietic cells and CD31 which expresses in endothelial cells [24]. Metformin has been widely reported to promote osteogenic differentiation by several types of MSCs, such as those derived from bone marrow, placenta, umbilical cord blood, adipose tissue, and muscle [25][26][27][28].…”