Ischemic Injury-Specific Gene Expression in the Rat Spinal Cord Injury Model Using Hypoxia-Inducible System

Lee, Minhyung; Lee, Eun Su; Kim, Young Soo; Choi, Byung Hyune; Park, Sora; Park, Hyun Seon; Park, Hyung Chun; Kim, Sung Wan; Ha, Yoon

doi:10.1097/01.brs.0000190395.43772.f3

Cited by 39 publications

(31 citation statements)

References 22 publications

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“…VEGF has been widely investigated for ischemic disease gene therapy, since it is the most efficient angiogenic factor. VEGF gene therapy was evaluated in ischemic heart disease, stroke, spinal cord injury, limb ischemia, as well as transplanted islets (Takeshita et al 1994;Isner et al 1996;Vincent et al 2000;Wright et al 2001;Carmeliet and Storkebaum 2002;Lee et al 2005;Shen et al 2006;Choi et al 2007a,b). However, the safety problem of VEGF is not completely addressed for clinical application, since it can induce overgrowth of endothelial cells and hemangioma (Springer et al 1998;Lee et al 2000;Su et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Delivery of hypoxia-inducible VEGF gene to rat islets using polyethylenimine

Kim

Lee

Kang

et al. 2009

Journal of Drug Targeting

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Islet transplantation is a promising strategy for treatment of diabetes. However, islets are exposed to hypoxia in the process of isolation and transplantation and prone to apoptosis. Vascular endothelial growth factor (VEGF) gene transfer is one of the promising strategies to address this problem. However, VEGF expression in the cells under normoxia is undesirable since it may induce pathological angiogenesis. Therefore, VEGF expression should be regulated to avoid this problem. In this study, hypoxia-inducible VEGF gene was transferred to islets using a non-viral carrier. Rat islets were transfected with high molecular weight PEI (25 kDa, PEI25K), low molecular weight PEI (2 kDa, PEI2K), and polyamidoamine dendrimer (PAMAM). PEI25K had higher transfection efficiency to rat islets than PAMAM or PEI2K. The hypoxia-inducible gene expression vector, pRTP801-Luc or pRTP801-VEGF was transferred to rat islets using PEI25K. Transfection assay with pRTP801-Luc showed that luciferase expression was induced in rat islets under hypoxia. In addition, transfer of pRTP801-VEGF showed that VEGF gene expression was higher under hypoxia than normoxia in rat islets. In conclusion, delivery of pRTP801-VEGF using PEI25K induces VEGF level specifically under hypoxia and may be useful for the development of anti-apoptotic strategies for islet transplantation.

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Section: Introductionmentioning

confidence: 99%

Delivery of hypoxia-inducible VEGF gene to rat islets using polyethylenimine

Kim

Lee

Kang

et al. 2009

Journal of Drug Targeting

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“…The secondary model comprises the posttraumatic ischemic changes, loss of energetic metabolism, edema, free radicals, electrolytic changes as intracellular calcium increase. These secondary changes are reversible and determine the therapeutic strategies [14][15][16][17].…”

Section: Discussionmentioning

confidence: 99%

Critical ischemia time in a model of spinal cord section. A study performed on dogs

et al. 2006

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Vascular changes after acute spinal cord trauma are important factors that predispose quadriplegia, in most cases irreversible. Repair of the spinal blood flow helps the spinal cord recovery. The average time to arrive and perform surgery is 3 h in most cases. It is important to determine the critical ischemia time in order to offer better functional prognosis. A spinal cord section and vascular clamping of the spinal anterior artery at C5-C6 model was used to determine critical ischemia time. The objective was to establish a critical ischemia time in a model of acute spinal cord section. Four groups of dogs were used, anterior approach and vascular clamp of spinal anterior artery with 1, 2, 3, and 4 h of ischemia and posterior hemisection of spinal cord at C5-C6 was performed. Clinical evaluation was made during 12 weeks and morphological evaluation at the end of this period. We obtained a maximal neurological coordination at 23 days average. Two cases showed sequels of right upper limb paresis at 1 and 3 ischemia hours. There was nerve conduction delay of 56% at 3 h of ischemia. Morphological examination showed 25% of damaged area. The VIII and IX Rexed's laminae were the most affected. The critical ischemia time was 3 h. Dogs with 4 h did not exhibit any recovery.

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“…For example, the erythropoietin (Epo) enhancersimian virus 40 (SV40) and RTP801 promoters were developed to regulate transcription under hypoxic stress (8)(9)(10). Hypoxia specifically activates these transcriptional systems in vitro, which favors their use to promote angiogenesis in ischemic myocardium and injured spinal cord (8,11).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Inducible Vascular Endothelial Growth Factor Gene Therapy Using the Oxygen-Dependent Degradation Domain in Myocardial Ischemia

et al. 2010

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Ischemic Injury-Specific Gene Expression in the Rat Spinal Cord Injury Model Using Hypoxia-Inducible System

Abstract: The pEpo-SV-Luc and pRTP801-Luc systems are effective in that they induce gene expression specifically in neurons under the hypoxic condition and spinal cord injury.

Cited by 39 publications

References 22 publications

Delivery of hypoxia-inducible VEGF gene to rat islets using polyethylenimine

Delivery of hypoxia-inducible VEGF gene to rat islets using polyethylenimine

Critical ischemia time in a model of spinal cord section. A study performed on dogs

Hypoxia-Inducible Vascular Endothelial Growth Factor Gene Therapy Using the Oxygen-Dependent Degradation Domain in Myocardial Ischemia

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