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

作者：Oh Jinsoo; You Youngsang; Yun Yeomin; Lee Hye Lan; Yoon Do Heum; Lee Minhyung; Ha Yoon^*

来源：Yonsei Medical Journal, 2015, 56(4): 1036-1043.

DOI：10.3349/ymj.2015.56.4.1036

• Neuronal cell type-inducible transgene expression
• neural stem cells
• combined treatment strategy
• 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.

• 出版日期2015-7-1