Yonsei Med J.  2015 Jul;56(4):1036-1043. 10.3349/ymj.2015.56.4.1036.

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

Affiliations
  • 1Department of Neurosurgery, Spine & Spinal Cord Institute and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. hayoon@yuhs.ac
  • 2Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.

Abstract

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.

Keyword

Neuronal cell type-inducible transgene expression; neural stem cells; combined treatment strategy; spinal cord injury

MeSH Terms

Cell Differentiation/genetics/physiology
*Gene Expression
Gene Regulatory Networks
*Genetic Therapy
Humans
Luciferases/genetics/*metabolism
*Neural Stem Cells
Neurons/metabolism
Phosphopyruvate Hydratase/metabolism
Promoter Regions, Genetic
Spinal Cord Injuries/*therapy
Stem Cells/*metabolism
Luciferases
Phosphopyruvate Hydratase
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