Development of neuronal cell-type inducible GM-CSF gene expression system and combined cell therapy in spinal cord injury model
Authors
유영상
Issue Date
2015
Description
Dept. of Medical Science/석사
Abstract
Promising therapy is needed to treat spinal cord injury (SCI) associated with permanent neurological damage. It is difficult to expect a sufficient therapeutic outcome by a single treatment method. Therefore, a strategy combining two or more techniques might be better for improving therapeutic effects.In this study, it was designed that a merged treatment strategy using neural stem cells (NSCs) introduced with neuronal cell-type inducible transgene expression system controlled by a neuronal specific enolase (NSE) promoter to maximize the therapeutic efficiency. 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 with a neuronal cell-type inducible luciferase expression system (NSE-Luci) or with a general luciferase expression system (SV-Luci) were measured and compared in vitro and in vivo.After verified neuronal cell-specific gene expression by luciferase gene, therapeutic gene, GM-CSF, was substituted with luciferase gene. Neuronal cell type-inducible GM-CSF expression system (NSE-GMCSF) compared with a general GM-CSF expression system (SV-GMCSF) in vitro and in vivo. The results show that neural stem cells introduced with a neuronal cell-type inducible luciferase expression system (NSE-Luci) showed a high level of luciferase expression compared to neural stem cells introduced with a general luciferase expression system (SV-Luci). And also therapeutic gene system, a neuronal cell-type inducible GM-CSF expression system (NSE-GMCSF) was higher expressed GM-CSF than a general GM-CSF expression system (SV-GMCSF). A neuronal cell-type inducible gene expression system has been demonstrated that it’s suitable for NSCs in a merged-treatment strategy. Therefore, it is suggested that this merged-treatment strategy based on NSCs and a neuronal
cell-type–inducible gene expression system is a promising tool for treatment of neurodegenerative disorder, including SCI.