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Evaluation the effect of metformin on proliferation, neurotrophic expression and antioxidant activity of mesenchymal stem cells

Samyra Sistani, Abootaleb Kosha, Mohammad Taghi Ghorbanian

Metformin is considered cheap, safe and efficient medication worldwide, which is used as a first-line treatment for type 2 diabetes, has exhibited great interest for its potential antiaging properties. There is increasing evidence that metformin can be used in a variety of therapeutic conditions due to its biological effect. Much attention has been paid to improving culture conditions, increasing the capacity and capability of Mesenchymal Stem Cells (MSCs). In this study, the viability and cell proliferation rate, antioxidant enzyme activity‚ and expression of neurotrophic genes at passage 3 of metformin-treated rat Bone marrow Mesenchymal Stem Cells (BMSCs) were evaluated.

BMSCs were isolated and treated with 1, 5, 10, 15, and 50 μM of metformin for 24 h. Then the survival rate of cells was measured by MTT assay. The growth rate and proliferation of cells at 24 hours after culture were assessed by Bromodeoxyuridine (BrdU) markers. Superoxide Dismutase (SOD) enzyme activity, Glutathione Peroxidase (GPX), and Malondialdehyde (MDA) levels were measured. Expression of neurotrophic factors Brain-Derived Neurotrophic Factor (BDNF), Glial cell-line Derived Neurotrophic Factor (GDNF) and Neurotrophin-3 (NT3) were also determined by Reverse Transcription Polymerase Chain Reaction (RTPCR).

The results of this study indicate that the proliferation rate by BrdU markers at 5 and 15 μM metformin showed a significant increase compared to control groups (P<0.5). Gene expression density of neurotrophic factors (NFs) showed that, there were significant differences between MSCs treatment groups and control group (P<0.5). Also, metformin-treated cell groups showed a higher antioxidant capacity than the control group. Metformin may be suggested as a pre-therapist to strengthen mesenchymal stem cells before transplantation for the treatment of neurodegenerative diseases.