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Development of neural stem cell line using hypoxia-inducible gene expression system

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dc.contributor.author정성삼-
dc.date.accessioned2015-12-24T08:31:49Z-
dc.date.available2015-12-24T08:31:49Z-
dc.date.issued2011-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/133622-
dc.descriptionDept. of Medicine/박사-
dc.description.abstractNonviral 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.statementOfResponsibilityopen-
dc.publisherGraduate School, Yonsei University-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleDevelopment of neural stem cell line using hypoxia-inducible gene expression system-
dc.title.alternative저산소 특이적 유전자 발현 시스템을 이용한 신경줄기세포주의 개발-
dc.typeThesis-
dc.contributor.alternativeNameJung, Sung Sam-
dc.type.localDissertation-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 3. Dissertation

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