Antiapoptotic effect of highly secreted GMCSF from neuronal cell-specific GMCSF overexpressing neural stem cells in spinal cord injury model

Youngsang You, Lihua Che, Hye Yeong Lee, Hye Lan Lee, Yeomin Yun, Minhyung Lee, Jinsoo Oh, Yoon Ha

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Study Design. Neuronal cell-specific gene expression system and neural stem cells (NSCs) were combined for treatment of spinal cord injury (SCI). Objective. To verify the reproducibility of the neuronal cellspecific therapeutic gene overexpression system, we develop a neuronal cell-specific granulocyte-macrophage colony-stimulating factor expression system (NSE-GMCSF), and then examine the characteristics of GMCSF overexpression and protective effect on neural cells in vitro and vivo. Summary of Background Data. The stem cell transplantation is considered a promising therapy for SCI. However, stem cell monotherapy strategy is insufficient for complete recovery after SCI. Therefore, combined treatment method based on stem cells with other therapeutic system may be effective for improving the therapeutic efficacy. In this study, we established the gene and stem cell therapy platform based on NSCs and neuronal cellspecific gene expression system. Methods. To examine the GMCSF expression pattern, we compared the amount of secreted GMCSF from the neuronal cell-specific GMCSF expressing NSCs with control GMCSF-expressing NSCs (respectively, NSE-GMCSF-NSCs vs. SVGMCSF- NSCs) by ELISA in vitro and in vivo, and then verified the neuronal protective effect of these cells in vitro and vivo. Results. The results showed that NSE-GMCSF-NSCs secreted more GMCSF compared with SV-GMCSF-NSCs in normoxia, hypoxia and cytotoxic conditions. The cell viability of NSEGMCSF- NSCs was increased depending on the amount of secreted GMCSF in cytotoxic condition. In addition, the amount of secreted GMCSF by NSE-GMCSF-NSCs transplanted into injured spinal cord was significantly higher than SV-GMCSFNSCs. Higher amount of secreted GMCSF decreased the expression of proapoptotic protein, Bax. Conclusion. In this study, we demonstrated that the neuronal cell-specific gene expression system induced overexpression of GMCSF in NSCs. These combined NSCs & gene therapy treatment protocol would be an effective therapeutic system for SCI.

Original languageEnglish
Pages (from-to)E1284-E1291
JournalSpine
Volume40
Issue number24
DOIs
Publication statusPublished - 2015 Jan 1

Fingerprint

Neural Stem Cells
Spinal Cord Injuries
Granulocyte-Macrophage Colony-Stimulating Factor
Stem Cells
Gene Expression
Therapeutics
Stem Cell Transplantation
Clinical Protocols
Cell- and Tissue-Based Therapy
Genetic Therapy
Genes
Cell Survival
Spinal Cord
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Clinical Neurology

Cite this

You, Youngsang ; Che, Lihua ; Lee, Hye Yeong ; Lee, Hye Lan ; Yun, Yeomin ; Lee, Minhyung ; Oh, Jinsoo ; Ha, Yoon. / Antiapoptotic effect of highly secreted GMCSF from neuronal cell-specific GMCSF overexpressing neural stem cells in spinal cord injury model. In: Spine. 2015 ; Vol. 40, No. 24. pp. E1284-E1291.
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title = "Antiapoptotic effect of highly secreted GMCSF from neuronal cell-specific GMCSF overexpressing neural stem cells in spinal cord injury model",
abstract = "Study Design. Neuronal cell-specific gene expression system and neural stem cells (NSCs) were combined for treatment of spinal cord injury (SCI). Objective. To verify the reproducibility of the neuronal cellspecific therapeutic gene overexpression system, we develop a neuronal cell-specific granulocyte-macrophage colony-stimulating factor expression system (NSE-GMCSF), and then examine the characteristics of GMCSF overexpression and protective effect on neural cells in vitro and vivo. Summary of Background Data. The stem cell transplantation is considered a promising therapy for SCI. However, stem cell monotherapy strategy is insufficient for complete recovery after SCI. Therefore, combined treatment method based on stem cells with other therapeutic system may be effective for improving the therapeutic efficacy. In this study, we established the gene and stem cell therapy platform based on NSCs and neuronal cellspecific gene expression system. Methods. To examine the GMCSF expression pattern, we compared the amount of secreted GMCSF from the neuronal cell-specific GMCSF expressing NSCs with control GMCSF-expressing NSCs (respectively, NSE-GMCSF-NSCs vs. SVGMCSF- NSCs) by ELISA in vitro and in vivo, and then verified the neuronal protective effect of these cells in vitro and vivo. Results. The results showed that NSE-GMCSF-NSCs secreted more GMCSF compared with SV-GMCSF-NSCs in normoxia, hypoxia and cytotoxic conditions. The cell viability of NSEGMCSF- NSCs was increased depending on the amount of secreted GMCSF in cytotoxic condition. In addition, the amount of secreted GMCSF by NSE-GMCSF-NSCs transplanted into injured spinal cord was significantly higher than SV-GMCSFNSCs. Higher amount of secreted GMCSF decreased the expression of proapoptotic protein, Bax. Conclusion. In this study, we demonstrated that the neuronal cell-specific gene expression system induced overexpression of GMCSF in NSCs. These combined NSCs & gene therapy treatment protocol would be an effective therapeutic system for SCI.",
author = "Youngsang You and Lihua Che and Lee, {Hye Yeong} and Lee, {Hye Lan} and Yeomin Yun and Minhyung Lee and Jinsoo Oh and Yoon Ha",
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Antiapoptotic effect of highly secreted GMCSF from neuronal cell-specific GMCSF overexpressing neural stem cells in spinal cord injury model. / You, Youngsang; Che, Lihua; Lee, Hye Yeong; Lee, Hye Lan; Yun, Yeomin; Lee, Minhyung; Oh, Jinsoo; Ha, Yoon.

In: Spine, Vol. 40, No. 24, 01.01.2015, p. E1284-E1291.

Research output: Contribution to journalArticle

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AU - You, Youngsang

AU - Che, Lihua

AU - Lee, Hye Yeong

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AU - Yun, Yeomin

AU - Lee, Minhyung

AU - Oh, Jinsoo

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AB - Study Design. Neuronal cell-specific gene expression system and neural stem cells (NSCs) were combined for treatment of spinal cord injury (SCI). Objective. To verify the reproducibility of the neuronal cellspecific therapeutic gene overexpression system, we develop a neuronal cell-specific granulocyte-macrophage colony-stimulating factor expression system (NSE-GMCSF), and then examine the characteristics of GMCSF overexpression and protective effect on neural cells in vitro and vivo. Summary of Background Data. The stem cell transplantation is considered a promising therapy for SCI. However, stem cell monotherapy strategy is insufficient for complete recovery after SCI. Therefore, combined treatment method based on stem cells with other therapeutic system may be effective for improving the therapeutic efficacy. In this study, we established the gene and stem cell therapy platform based on NSCs and neuronal cellspecific gene expression system. Methods. To examine the GMCSF expression pattern, we compared the amount of secreted GMCSF from the neuronal cell-specific GMCSF expressing NSCs with control GMCSF-expressing NSCs (respectively, NSE-GMCSF-NSCs vs. SVGMCSF- NSCs) by ELISA in vitro and in vivo, and then verified the neuronal protective effect of these cells in vitro and vivo. Results. The results showed that NSE-GMCSF-NSCs secreted more GMCSF compared with SV-GMCSF-NSCs in normoxia, hypoxia and cytotoxic conditions. The cell viability of NSEGMCSF- NSCs was increased depending on the amount of secreted GMCSF in cytotoxic condition. In addition, the amount of secreted GMCSF by NSE-GMCSF-NSCs transplanted into injured spinal cord was significantly higher than SV-GMCSFNSCs. Higher amount of secreted GMCSF decreased the expression of proapoptotic protein, Bax. Conclusion. In this study, we demonstrated that the neuronal cell-specific gene expression system induced overexpression of GMCSF in NSCs. These combined NSCs & gene therapy treatment protocol would be an effective therapeutic system for SCI.

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