Effects of Reactive Oxygen Species on Differentiation of Bone Marrow Mesenchymal Stem Cells
1Department of Orthopaedic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
Abstract:
BACKGROUND The low differentiation rates for transplanted stem cells are challenging problems in spinal cord injury (SCI) treatment. Studies have demonstrated that the inhibition of the Notch1 pathway in bone marrow mesenchymal stem cells (BMSCs) contributed to the differentiation of these cells. Research findings that certain antioxidants induce BMSCs to differentiate into neuronal cells suggest that BMSC differentiation is related to the level of reactive oxygen species (ROS) in cells. This study aimed to define the effect of ROS on the differentiation of BMSCs. MATERIAL AND METHODS In this study, after BMSCs were induced with the antioxidant β-mercaptoethanol (β-ME), related proteins were analyzed by Western blotting and immunofluorescence. In order to find the role of ROS in the differentiation, DCFH-DA was used to detect ROS levels in antioxidant-treated BMSCs, H2O2-treated BMSCs, and normal BMSCs, and the expression levels of Notch1 and its downstream transcriptional suppressor Hes1 were analyzed. RESULTS Induced with β-ME, Western blotting and immunofluorescence revealed gradual increases in the expression of Nestin (a neural stem cell-specific protein) and neuron-specific enolase (NSE) but decreases in Notch1 expression. The expression levels of Notch1 and Hes1 were positively correlated with changes in ROS level. CONCLUSIONS These data suggest that the antioxidant-induced differentiation of BMSCs into neurons may be related to ROS-based regulation of the Notch1 signalling pathway.
Insights
Antioxidants promote bone marrow mesenchymal stem cells (BMSCs) to differentiate into neurons by regulating reactive oxygen species (ROS) levels and the Notch1 signaling pathway. This finding offers new insights for spinal cord injury (SCI) treatment.
Area of Science:
- Biomedical Engineering
- Stem Cell Biology
- Neuroscience
Background:
- Low differentiation rates of transplanted stem cells pose challenges in spinal cord injury (SCI) treatment.
- Inhibiting the Notch1 pathway in bone marrow mesenchymal stem cells (BMSCs) promotes their differentiation.
- Antioxidants may induce BMSC differentiation into neuronal cells, suggesting a role for reactive oxygen species (ROS).
Purpose of the Study:
- To investigate the effect of reactive oxygen species (ROS) on the differentiation of bone marrow mesenchymal stem cells (BMSCs).
- To explore the relationship between ROS levels and the Notch1 signaling pathway in BMSC differentiation.
Main Methods:
- Bone marrow mesenchymal stem cells (BMSCs) were treated with the antioxidant β-mercaptoethanol (β-ME).
- Protein expression (Nestin, NSE, Notch1, Hes1) was analyzed using Western blotting and immunofluorescence.
- Reactive oxygen species (ROS) levels were measured using DCFH-DA in normal, antioxidant-treated, and H2O2-treated BMSCs.
Main Results:
- β-ME induction increased Nestin and neuron-specific enolase (NSE) expression, indicating neuronal differentiation.
- Notch1 expression decreased following β-ME treatment.
- Notch1 and Hes1 expression levels showed a positive correlation with changes in ROS levels.
Conclusions:
- Antioxidant-induced differentiation of BMSCs into neurons appears to be mediated by ROS-based regulation of the Notch1 signaling pathway.
- This study provides a potential mechanism for enhancing stem cell therapy in spinal cord injury.
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