The Effect of AdipoRon on the Activity of Caspase 3, Matrix Metalloproteinases 2 and 9, and Angiogenesis in Rat Bone Marrow-Derived Mesenchymal Stem Cell

Today, the use of mesenchymal stem cells (MSCs) is an appropriate option for the treatment of many diseases. But, poor viability, and low number of transplanted stem cells are the main obstacles in cell therapy. Recently, stem cell preconditioning with chemical and pharmacological agents has been shown to increase therapeutic efficacy. Herein, we investigated the effect of AdipoRon, adiponectin receptor agonist, on activity of caspase 3, matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), and angiogenesis in rat bone marrow-derived mesenchymal stem cells.
Mesenchymal stem cells were treated with different concentrations of AdipoRon for 24 hours. The expression level of vascular endothelial growth factor (VEGF), and angiopoietin 2 and 4 (Ang-2 and Ang-4) were assessed using real-time polymerase chain reaction (real-time PCR). Gelatin zymography assay was applied to investigate the protease activity of matrix metalloproteinase 2 and 9. Measurement of caspase-3 activity was carried out via an enzymatic assay.
Findings: The real-time polymerase chain reaction results indicated that the expression of vascular endothelial growth factor was higher in AdipoRon-treated mesenchymal stem cells compared to control groups when angiopoietin 2 and 4 did not show any significant change. The enzymatic activity of metalloproteinase 2 and 9 was increased in treated samples with AdipoRon compared to control group. The caspase-3 activity was attenuated in AdipoRon-pretreated cells compared to the control group.
Based on these results, it is likely that preconditioning of mesenchymal stem cells with AdipoRon prior to transplantation can enhance the viability and migration via overexpression of vascular endothelial growth factor, activation of metalloproteinase 2 and 9 enzymes, and inhibit the activation of caspase-3.