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A Gene and Neural Stem Cell Therapy Platform Based on Neuronal Cell Type-Inducible Gene Overexpression

 Jinsoo Oh  ;  Youngsang You  ;  Yeomin Yun  ;  Hye-Lan Lee  ;  Do Heum Yoon  ;  Minhyung Lee  ;  Yoon Ha 
 YONSEI MEDICAL JOURNAL, Vol.56(4) : 1036-1043, 2015 
Journal Title
Issue Date
Cell Differentiation/genetics ; Cell Differentiation/physiology ; Gene Expression* ; Gene Regulatory Networks ; Genetic Therapy* ; Humans ; Luciferases/genetics ; Luciferases/metabolism* ; Neural Stem Cells* ; Neurons/metabolism ; Phosphopyruvate Hydratase/metabolism ; Promoter Regions, Genetic ; Spinal Cord Injuries/therapy* ; Stem Cells/metabolism*
Neuronal cell type-inducible transgene expression ; combined treatment strategy ; neural stem cells ; spinal cord injury
PURPOSE: Spinal cord injury (SCI) is associated with permanent neurological damage, and treatment thereof with a single modality often does not provide sufficient therapeutic outcomes. Therefore, a strategy that combines two or more techniques might show better therapeutic effects. MATERIALS AND METHODS: In this study, we designed a combined treatment strategy based on neural stem cells (NSCs) introduced via a neuronal cell type-inducible transgene expression system (NSE::) controlled by a neuron-specific enolase (NSE) promoter to maximize therapeutic efficiency and neuronal differentiation. The luciferase gene was chosen to confirm whether this combined system was working properly prior to using a therapeutic gene. The luciferase expression levels of NSCs introduced via the neuronal cell type-inducible luciferase expression system (NSE::Luci) or via a general luciferase expressing system (SV::Luci) were measured and compared in vitro and in vivo. RESULTS: NSCs introduced via the neuronal cell type-inducible luciferase expressing system (NSE::Luci-NSCs) showed a high level of luciferase expression, compared to NSCs introduced via a general luciferase expressing system (SV::Luci-NSCs). Interestingly, the luciferase expression level of NSE::Luci-NSCs increased greatly after differentiation into neurons. CONCLUSION: We demonstrated that a neuronal cell type-inducible gene expression system is suitable for introducing NSCs in combined treatment strategies. We suggest that the proposed strategy may be a promising tool for the treatment of neurodegenerative disorders, including SCI.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Do Heum(윤도흠) ORCID logo https://orcid.org/0000-0003-1452-5724
Ha, Yoon(하윤)
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