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Combined Method of Neuronal Cell-Inducible Vector and Valproic Acid for Enhanced Gene Expression under Hypoxic Conditions

Authors
 Yeomin Yun  ;  Daye Baek  ;  Dongsu Lee  ;  Eunji Cheong  ;  Janghwan Kim  ;  Jinsoo Oh  ;  Yoon Ha 
Citation
 TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Vol.17(1) : 55-66, 2020-02 
Journal Title
 TISSUE ENGINEERING AND REGENERATIVE MEDICINE 
ISSN
 1738-2696 
Issue Date
2020-02
Keywords
Hypoxia ; Induced neural stem cells (iNSCs) ; Neuron-specific enolase promoter (pNSE) ; Spinal cord injury (SCI) ; Valproic acid (VPA)
Abstract
Background: Gene therapy shows the ability to restore neuronal dysfunction via therapeutic gene expression. The efficiency of gene expression and delivery to hypoxic injury sites is important for successful gene therapy. Therefore, we established a gene/stem cell therapy system using neuron-specific enolase promoter and induced neural stem cells in combination with valproic acid to increase therapeutic gene expression in hypoxic spinal cord injury. Methods: To examine the effect of combined method on enhancing gene expression, we compared neuronal cell-inducible luciferase levels under normoxia or hypoxia conditions in induced neural stem cells with valproic acid. Therapeutic gene, vascular endothelial growth factor, expression with combined method was investigated in hypoxic spinal cord injury model. We verified gene expression levels and the effect of different methods of valproic acid administration in vivo. Results: The results showed that neuron-specific enolase promoter enhanced gene expression levels in induced neural stem cells compared to Simian Virus 40 promoter under hypoxic conditions. Valproic acid treatment showed higher gene expression of neuron-specific enolase promoter than without treatment. In addition, gene expression levels and cell viability were different depending on the various concentration of valproic acid. The gene expression levels were increased significantly when valproic acid was directly injected with induced neural stem cells in vivo. Conclusion: In this study, we demonstrated that the combination of neuron-specific enolase promoter and valproic acid induced gene overexpression in induced neural stem cells under hypoxic conditions and also in spinal cord injury depending on valproic acid administration in vivo. Combination of valproic acid and neuron-specific enolase promoter in induced neural stem cells could be an effective gene therapy system for hypoxic spinal cord injury.
Full Text
https://link.springer.com/article/10.1007/s13770-019-00223-w
DOI
10.1007/s13770-019-00223-w
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Ha, Yoon(하윤)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180236
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