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

• Published in: Yonsei medical journal Vol. 56; no. 4; pp. 1036 - 1043
• Main Authors: Oh, Jinsoo, You, Youngsang, Yun, Yeomin, Lee, Hye-Lan, Yoon, Do Heum, Lee, Minhyung, Ha, Yoon
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.07.2015; 연세대학교의과대학
• Subjects: Cell Differentiation - genetics; Cell Differentiation - physiology; Gene Expression; Gene Regulatory Networks; Genetic Therapy; Humans; Luciferases - genetics; Luciferases - metabolism; Neural Stem Cells; Neurons - metabolism; Original; Phosphopyruvate Hydratase - metabolism; Promoter Regions, Genetic; Spinal Cord Injuries - therapy; Stem Cells - metabolism; 의학일반; spinal cord injury; Neuronal cell type-inducible transgene expression; neural stem cells; combined treatment strategy
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2015.56.4.1036

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. 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. 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. 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.