Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury

H. J. Kim, J. S. Oh, S. S. An, W. A. Pennant, S. J. Gwak, A. N. Kim, P. K. Han, D. H. Yoon, K. N. Kim, Y. Ha

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Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that stimulates the differentiation and function of hematopoietic cells. GM-CSF has been implicated in nervous system function. The goal of the present study was to understand the effects of hypoxia-induced GM-CSF on neural stem cells (NSCs) in a model of spinal cord injury (SCI). GM-CSF-overexpressing NSCs were engineered utilizing a hypoxia-inducible gene expression plasmid, including an Epo enhancer ahead of an SV promoter (EpoSV-GM-CSF). Cells were then subjected to hypoxia (pO 2, 1%) or a hypoxia-mimicking reagent (CoCl 2) in vitro. The progression of time of GM-CSF expression was tracked in EpoSV-GM-CSF-transfected NSCs. Overexpression of GM-CSF in undifferentiated and differentiated NSCs created resistance to H 2 O 2-induced apoptosis in hypoxia. NSCs transfected with EpoSV-GM-CSF or SV-GM-CSF were transplanted into rats after SCI to assess the effect of GM-CSF on NSC survival and restoration of function. Moreover, a significantly higher amount of surviving NSCs and neuronal differentiation was observed in the EpoSV-GM-CSF-treated group. Significant improvement in locomotor function was also found in this group. Thus, GM-CSF overexpression by the Epo enhancer in hypoxia was beneficial to transplanted NSC survival and to behavioral improvement, pointing toward a possible role for GM-CSF in the treatment of SCI.

Original languageEnglish
Pages (from-to)513-521
Number of pages9
JournalGene Therapy
Volume19
Issue number5
DOIs
Publication statusPublished - 2012 May 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Kim, H. J., Oh, J. S., An, S. S., Pennant, W. A., Gwak, S. J., Kim, A. N., Han, P. K., Yoon, D. H., Kim, K. N., & Ha, Y. (2012). Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury. Gene Therapy, 19(5), 513-521. https://doi.org/10.1038/gt.2011.137