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Development of neural stem cell line using hypoxia-inducible gene expression system
DC Field | Value | Language |
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dc.contributor.author | 정성삼 | - |
dc.date.accessioned | 2015-12-24T08:31:49Z | - |
dc.date.available | 2015-12-24T08:31:49Z | - |
dc.date.issued | 2011 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/133622 | - |
dc.description | Dept. of Medicine/박사 | - |
dc.description.abstract | Nonviral ex vivo local gene therapy systems consisting of regulated gene expression vectors and cellular delivery platforms represent a novel strategy for tissue repair and regeneration. We introduced a hypoxia-regulated plasmid-based system into mouse neural stem cells (NSCs) as an efficient gene expression and delivery platform for rapid, robust and persistent hypoxic/ischemic-regulated gene expression in the spinal cord. A synthetic hypoxia-responsive erythropoietin (Epo) enhancer, the SV40 minimal promoter and the luciferase (Luc) reporter gene were incorporated in a DsRed-expressing double-promoter plasmid for cell lipofection and Zeocin-selection to establish a hypoxia-regulated stable NSC line (NSC-Epo-SV-Luc). A non-hypoxia-regulated stable NSC line (NSC-SV-Luc) was also established as a control. Under the transcriptional regulation of the Epo enhancer, in vitro luciferase expression in NSC-Epo-SV-Luc, but not in NSC-SV-Luc, was sensitively augmented according to the strength and duration of the hypoxic stimulus and was quickly down-regulated to a low basal level after reoxygenation of the hypoxic cells. Furthermore, deoxygenation of the reoxygenated cells clearly enhanced the luciferase activity again. After transplantation into a rat spinal cord injury (SCI) model, only NSC-Epo-SV-Luc showed ischemic injury-specific luciferase expression Notably, the engineered NSC lines maintained the neural differentiation potential and retained the hypoxia-regulated luciferase expression after differentiation. We propose that NSCs engineered with the Epo-SV-therapeutic gene will be valuable for developing a controllable stem cell-mediated nonviral gene therapy for SCI or other central nervous system diseases accompanied with chronic or episodic hypoxic/ischemic stresses. | - |
dc.description.statementOfResponsibility | open | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Development of neural stem cell line using hypoxia-inducible gene expression system | - |
dc.title.alternative | 저산소 특이적 유전자 발현 시스템을 이용한 신경줄기세포주의 개발 | - |
dc.type | Thesis | - |
dc.contributor.alternativeName | Jung, Sung Sam | - |
dc.type.local | Dissertation | - |
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