N-Acetyl cysteine protects diabetic mouse derived mesenchymal stem cells from hydrogen-peroxide-induced injury: A novel hypothesis for autologous stem cell transplantation

Abstract

BackgroundStem cell transplantation is one of the therapeutic options available to repair damaged organs. However, transplanted cells entail several challenges including their survival in diabetes-affected injured tissue. This study was designed to determine the effects of preconditioning of mesenchymal stem cells (MSCs) with N-acetyl cysteine (NAC), a widely used antioxidant drug. MethodsDiabetic-mouse-derived MSCs (blood glucose≥300 mg/dL) were preconditioned with 30mM NAC for 1 hour followed by oxidative injury with 100μM hydrogen peroxide (H2O2) for 1 hour. ResultsGene expression analysis showed marked upregulation of prosurvival genes (Akt and Bcl-2) and significantly downregulated expression of proapoptotic and stress genes (Capase-3, Bax, Bak, p53, p38, and NF-κB) in the 30mM-NAC-treated group when compared with those cells treated with H2O2 alone. NAC preconditioning improved cell viability, decreased lactate dehydrogenase release, β-galactosidase activity, and Annexin-V-positive cells. Also, amelioration of oxidative stress, as shown by a decrease in malondialdehyde level and an increase in superoxide dismutase and catalase activities and glutathione level, was observed in the 30mM-NAC-treated group in comparison to cells treated with H2O2 alone. ConclusionThis study demonstrates the potential benefits of pharmacological preconditioning of diabetic-mouse-derived MSCs with NAC for amelioration of apoptosis and oxidative stress in H2O2 induced injury.