Document Type : Original Article
Department of Pharmacology and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
Razi Drug Research Center, Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
Department of Pharmacology, Semnan University of Medical Science, Semnan, Iran
Objective: This study aimed to investigate the reliability of diabetic adipose-derived stem cells (ADSCs) for autologous
cell-based therapies by exploring the functionality of signalling pathways involved in regulating oxidative stress and
Materials and Methods: In this experimental study, ADSCs were isolated from streptozotocin (STZ)-induced diabetic
rats (dADSCs) and normal rats (nADSCs). The colonies derived from dADSCs and nADSCs were compared by colony-forming unit (CFU) assay. Reactive oxygen species (ROS) formation and total antioxidant power (TAP) were also measured. Furthermore, the expression of antioxidant enzymes, including catalase (Cat), superoxide dismutase (Sod)-1 and -3, glutathione peroxidase (Gpx)-1, -3 and -4 was measured at mRNA level by semi-quantitative reverse transcriptase polymerase chain reaction assay. The expression of Bax, Bcl2, caspase-3, total and phosphorylated c-Jun N-terminal kinase (JNK) and P38 Mitogen-Activated Protein Kinase (MAPK) at protein level was analyzed by western blotting.
Results: The results of this study indicated that viability and plating efficiency of dADSCs were significantly lower than
those of nADSCs. ROS generation and TAP level were respectively higher and lower in dADSCs. The gene expression of antioxidant enzymes, including Cat, Sod-1, Gpx-3 and Gpx-4 in dADSCs was significantly greater than that in nADSCs. However, Sod-3 and Gpx-1 mRNA levels were decreased in dADSCs. Moreover, Bax/Bcl-2 protein ratio, caspase-3 protein expression and phosphorylation of JNK and P38 proteins were increased in dADSCs compared to nADSCs.
Conclusion: Taken together, diabetes might impair the cellular functions of dADSCs as candidates for autologous cellbased therapies. This impairment seems to be mediated by JNK, P38 MAPKs, and mitochondria pathway of apoptosis
and partly by disruption of antioxidant capacity.