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

Yeomin Yun; Daye Baek; Dongsu Lee; Eunji Cheong; Janghwan Kim; Jinsoo Oh; Yoon Ha

doi:10.1007/s13770-019-00223-w

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

Yeomin Yun, Daye Baek, Dongsu Lee, Eunji Cheong, Janghwan Kim, Jinsoo Oh, Yoon Ha

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	55-66
Number of pages	12
Journal	Tissue Engineering and Regenerative Medicine
Volume	17
Issue number	1
DOIs	https://doi.org/10.1007/s13770-019-00223-w
Publication status	Published - 2020 Feb 1

Bibliographical note

Funding Information:
This work was partly supported by the Brain Korea 21 PLUS Project for Medical Science, Yonsei University; Basic Science Research Program through the National Research Foundation of Korea (NRF) (No. 2015R1D1A1A02059821); and a National Research Foundation of Korea Grant, funded by the Korean Government (NRF-2015R1A6A3A01018883). This research was also supported by grants from the National Research Foundation of Korea (2013M3A9B4076483 and 2016K1A3A1A61006001) and KRIBB research initiative program funded by the Ministry of Science and ICT.

Funding Information:
This work was partly supported by the Brain Korea 21 PLUS Project for Medical Science, Yonsei University; Basic Science Research Program through the National Research Foundation of Korea (NRF) (No. 2015R1D1A1A02059821); and a National Research Foundation of Korea Grant, funded by the Korean Government (NRF-2015R1A6A3A01018883). This research was also supported by grants from the National Research Foundation of Korea (2013M3A9B4076483 and 2016K1A3A1A61006001) and KRIBB research initiative program funded by the Ministry of Science and ICT.

Publisher Copyright:
© 2019, The Korean Tissue Engineering and Regenerative Medicine Society.

All Science Journal Classification (ASJC) codes

Medicine (miscellaneous)
Biomedical Engineering

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@article{b48927d613b045faaabd17ef95b6bf0c,

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

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.",

author = "Yeomin Yun and Daye Baek and Dongsu Lee and Eunji Cheong and Janghwan Kim and Jinsoo Oh and Yoon Ha",

note = "Funding Information: This work was partly supported by the Brain Korea 21 PLUS Project for Medical Science, Yonsei University; Basic Science Research Program through the National Research Foundation of Korea (NRF) (No. 2015R1D1A1A02059821); and a National Research Foundation of Korea Grant, funded by the Korean Government (NRF-2015R1A6A3A01018883). This research was also supported by grants from the National Research Foundation of Korea (2013M3A9B4076483 and 2016K1A3A1A61006001) and KRIBB research initiative program funded by the Ministry of Science and ICT. Funding Information: This work was partly supported by the Brain Korea 21 PLUS Project for Medical Science, Yonsei University; Basic Science Research Program through the National Research Foundation of Korea (NRF) (No. 2015R1D1A1A02059821); and a National Research Foundation of Korea Grant, funded by the Korean Government (NRF-2015R1A6A3A01018883). This research was also supported by grants from the National Research Foundation of Korea (2013M3A9B4076483 and 2016K1A3A1A61006001) and KRIBB research initiative program funded by the Ministry of Science and ICT. Publisher Copyright: {\textcopyright} 2019, The Korean Tissue Engineering and Regenerative Medicine Society.",

year = "2020",

month = feb,

day = "1",

doi = "10.1007/s13770-019-00223-w",

language = "English",

volume = "17",

pages = "55--66",

journal = "Tissue Engineering and Regenerative Medicine",

issn = "1738-2696",

publisher = "Springer Science + Business Media",

number = "1",

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Combined Method of Neuronal Cell-Inducible Vector and Valproic Acid for Enhanced Gene Expression under Hypoxic Conditions. / Yun, Yeomin; Baek, Daye; Lee, Dongsu; Cheong, Eunji; Kim, Janghwan; Oh, Jinsoo; Ha, Yoon.

In: Tissue Engineering and Regenerative Medicine, Vol. 17, No. 1, 01.02.2020, p. 55-66.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Combined Method of Neuronal Cell-Inducible Vector and Valproic Acid for Enhanced Gene Expression under Hypoxic Conditions

AU - Yun, Yeomin

AU - Baek, Daye

AU - Lee, Dongsu

AU - Cheong, Eunji

AU - Kim, Janghwan

AU - Oh, Jinsoo

AU - Ha, Yoon

N1 - Funding Information: This work was partly supported by the Brain Korea 21 PLUS Project for Medical Science, Yonsei University; Basic Science Research Program through the National Research Foundation of Korea (NRF) (No. 2015R1D1A1A02059821); and a National Research Foundation of Korea Grant, funded by the Korean Government (NRF-2015R1A6A3A01018883). This research was also supported by grants from the National Research Foundation of Korea (2013M3A9B4076483 and 2016K1A3A1A61006001) and KRIBB research initiative program funded by the Ministry of Science and ICT. Funding Information: This work was partly supported by the Brain Korea 21 PLUS Project for Medical Science, Yonsei University; Basic Science Research Program through the National Research Foundation of Korea (NRF) (No. 2015R1D1A1A02059821); and a National Research Foundation of Korea Grant, funded by the Korean Government (NRF-2015R1A6A3A01018883). This research was also supported by grants from the National Research Foundation of Korea (2013M3A9B4076483 and 2016K1A3A1A61006001) and KRIBB research initiative program funded by the Ministry of Science and ICT. Publisher Copyright: © 2019, The Korean Tissue Engineering and Regenerative Medicine Society.

PY - 2020/2/1

Y1 - 2020/2/1

N2 - 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.

AB - 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.

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DO - 10.1007/s13770-019-00223-w

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AN - SCOPUS:85076353753

VL - 17

SP - 55

EP - 66

JO - Tissue Engineering and Regenerative Medicine

JF - Tissue Engineering and Regenerative Medicine

SN - 1738-2696

IS - 1

ER -

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

Abstract

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