A Gene and Neural Stem Cell Therapy Platform Based on Neuronal Cell Type-Inducible Gene Overexpression |
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Authors: | Jinsoo Oh Youngsang You Yeomin Yun Hye-Lan Lee Do Heum Yoon Minhyung Lee Yoon Ha |
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Affiliation: | 1.Department of Neurosurgery, Spine & Spinal Cord Institute and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.;2.Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea. |
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Abstract: | PurposeSpinal 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 MethodsIn 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.ResultsNSCs 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.ConclusionWe 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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Keywords: | Neuronal cell type-inducible transgene expression neural stem cells combined treatment strategy spinal cord injury |
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