A Gene and Neural Stem Cell Therapy Platform Based on Neuronal Cell Type-Inducible Gene Overexpression.
10.3349/ymj.2015.56.4.1036
- Author:
Jinsoo OH
1
;
Youngsang YOU
;
Yeomin YUN
;
Hye Lan LEE
;
Do Heum YOON
;
Minhyung LEE
;
Yoon HA
Author Information
1. Department 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
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Neuronal cell type-inducible transgene expression;
neural stem cells;
combined treatment strategy;
spinal cord injury
- MeSH:
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
- From:Yonsei Medical Journal
2015;56(4):1036-1043
- CountryRepublic of Korea
- Language:English
-
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.
