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| 1 | Survival of transplanted neurotrophin-3 expressing human neural stem cells and motor function in a rat model of spinal cord injury显示文摘<正>BACKGROUND:Many methods have been attempted to repair nerves following spinal cord injury, including peripheral nerve transplantation,Schwann cell transplantation,olfactory ensheathing cell transplantation,and embryonic neural tissue transplantation.However,there is a need for improved outcomes. OBJECTIVE:To investigate the repair feasibility for rat spinal cord injury using human neural stem cells(hNSCs) genetically modified by lentivirus to express neurotrophin-3. DESIGN,TIME AND SETTING:In vitro cell biological experiment and in vivo randomized,controlled, genetic engineering experiment were performed at the Third Military Medical University of Chinese PLA and First People's Hospital of Yibin,China from March 2006 to December 2007. MATERIALS:A total of 64 adult,female,Wistar rats were used for the in vivo study.Of them,48 rats were used to establish models of spinal cord hemisection,and were subsequently equally and randomly assigned to model,genetically modified hNSC,and normal hNSC groups.The remaining 16 rats served as normal controls. METHODS:hNSCs were in vitro genetically modified by lentivirus to secrete both green fluorescence protein and neurotrophin-3.Neurotrophin-3 expression was measured by Western blot. Genetically modified hNSC or normal hNSC suspension(5×10~5) was injected into the rat spinal cord following T_(10) spinal cord hemisection.A total of 5μL Dulbecco's-modified Eagle's medium was infused into the rat spinal cord in the model group.Transgene expression and survival of transplanted hNSCs were determined by immunohistochemistry.Motor function was evaluated using the Basso,Beattie,and Bresnahan(BBB) scale. MAIN OUTCOME MEASURES:The following parameters were measured:expression of neurotrophin-3 produced by genetically modified hNSCs,transgene expression and survival of hNSCs in rats,motor function in rats. RESULTS:hNSCs were successfully genetically modified by lentivirus to stably express neurotrophin-3.The transplanted hNSCs primarily gathered at,or around,the injection site two weeks following transplantation,and gradually migrated towards the surrounding tissue. Transplanted hNSCs were observed 7.0-8.0 mm away from the injection site.In addition,hNSCs were observed 10 weeks after transplantation.At week 4,BBB locomotor scores were significantly greater in the genetically modified hNSC and normal hNSC groups,compared with the model group (P<0.05),and scores were significantly greater in the genetically modified hNSC group compared with the normal hNSC group(P<0.05). CONCLUSION:hNSCs were genetically modified with lentivirus to stably secrete neurotrophin-3. hNSCs improved motor function recovery in rats following spinal cord injury. | Peiqiang Cai Guangyun Sun Peishu Cai Martin Oudega Rui Xiao Xuewen Wang Wei Li Yunbing Shu Cheng Cai Haihao Yang Xuebing Shan Wuhua Luo | 2009 | Neural Regeneration Research2009，4，7： | 18 |
| 2 | Axonal regeneration after spinal cord injury in zebrafish and mammals: differences, similarities, translation显示文摘Spinal cord injury (SCI) in mammals results in functional deficits that are mostly permanent due in part to the inability of severed axons to regenerate. Several types of growth-inhibitory molecules expressed at the injury site contribute to this regeneration failure. The responses of axons to these inhibitors vary greatly within and between organisms, reflecting axons' characteristic intrinsic propensity for regeneration. In the zebrafish (Danio rerio) many but not all axons exhibit successful regeneration after SCi. This review presents and compares the intrinsic and extrinsic determinants of axonal regeneration in the injured spinal cord in mammals and zebrafish. A better understanding of the molecules and molecular pathways underlying the remarkable individualism among neurons in mature zebrafish may support the development of therapies for SCI and their translation to the clinic. | Katarina Vajn Jeffery A Plunkett Alexis Tapanes-Castillo Martin oudega | 2013 | Neuroscience Bulletin2013，29，4： | 9 |
| 3 | Biomaterials for spinal cord repair显示文摘Spinal cord injury (SCi) results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCi is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCi. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCi. A plethora of biomaterials is available and has been tested in various models of SCi. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCi. | Agnes E. Haggerty Martin oudega | 2013 | Neuroscience Bulletin2013，29，4： | 9 |
| 4 | 移植分泌神经营养因子-3的人胚神经干细胞对大鼠脊髓损伤后功能恢复的影响显示文摘目的探索Lentivirus介导神经营养因子(NT-3)转染的人胚神经干细胞(human neural stem cells,hNSCs)对大鼠损伤脊髓治疗机制和治疗的作用机制。方法在体外用Lentivirus构建同时表达绿色荧光蛋白(green fluorescence protein,GFP)和NT-3的hNSCs,将其移植到T10脊髓半横断损伤的大鼠体内,用荧光显微镜和BBB评分观察体内转基因表达和大鼠功能恢复情况,用免疫组化染色检测移植细胞在体内存活分化情况。结果(1)在体外用Lentivirus成功构建了同时表达多基因的人胚基因工程NSC并检测到了稳定的转基因表达;(2)用荧光显微镜可以检测到到hNSC,能在体内长时间存活并表达转基因;(3)BBB评分检测到hNSCs移植组大鼠后肢功能有明显恢复;(4)移植的基因工程hNSC能在体内分化为神经元及星形胶质细胞等功能细胞。结论Lentivirus介导NT-3转染的hNSC能够调整损伤的局部微环境促进损伤脊髓的功能恢复。 | 孙广运 蔡培强 Oudega Martin 王学文 Blits Bas 舒运兵 蔡程 | 2007 | 中华创伤杂志2007，23，2： | 8 |
| 5 | GENETIC ENGINEERING NEURAL STEM CELL MODIFIED BY LENTIVIRUS FOR REPAIR OF SPINAL CORD INJURY IN RATS显示文摘Objective To explore the feasibility for therapy of spinal cord injury (SCI) by genetic engineering neural stem cell (NSC) modified by lentiviral vector. Methods Following the construction of the genetic engineering NSC modified by lentivirus to secrete both neurotrophic factor-3 (NT-3) and green fluorescence protein (GFP), hemisection of spinal cord at the level of T_ 10 was performed in 56 adult Wistar rats that were randomly divided into 4 groups (n=14), namely 3 therapeutic groups and 1 control group. The therapeutic groups were dealed with NSC, genetic engineering NSC, and concentrated lentiviral supernatant which carries both GFP and NT-3, respectively. Then used fluorescence microscope to detect the transgenic expression in vitro and in vivo, migration of the grafted cells in vivo, and used the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test to assess the recovery of function. Results The transplanted cells could survive for long time in vivo and migrate for long distance. The stable transgenic expression could be detected in vivo. The hindlimb function of the injured rats in 3 therapeutic groups, especially those dealed with genetic engineering NSC, improved obviously. Conclusion It is feasible to combine NSC with lentivirus for the repair of SCI. NSC modified by lentivirus to deliver NT-3, acting as a source of neurotrophic factors and function cell in vivo, has the potential to participate in spinal cord repair. | Xun Tang Pei-qiang Cai Yue-qiu Lin Martin Oudega Bas Blits Ling Xu Yun-kang Yang Tian-hua Zhou | 2006 | Chinese Medical Sciences Journal2006，21，2： | 8 |
| 6 | Lentivirus介导分泌神经营养因子-3的基因工程神经干细胞移植治疗脊髓损伤的实验研究显示文摘 | 蔡培强 汤逊 林月秋 Martin Oudega Bas Blits 徐林 阳运康 | 2005 | 中华外科杂志2005，43，16： | 4 |
| 7 | Lentivirus介导神经营养因子-3促进脊髓损伤大鼠功能恢复显示文摘目的探讨Lentivirus介导分泌神经营养因子-3(NT-3)直接体内转基因治疗大鼠脊髓损伤作用和机制。方法将28只Wistar大鼠在T10水平制成半横断损伤模型,随机分为体内转基因治疗组和损伤对照组,每组14只;用携带NT-3和绿色荧光蛋白(GFP)的Lentivirus对大鼠行直接体内转基因治疗;荧光显微镜观察体内转基因表达,后肢运动功能评分法(BBB评分)检测大鼠后肢功能恢复情况。结果用荧光显微镜检测到损伤脊髓内有较多的持续表达转基因的细胞;BBB评分结果显示,从伤后第4周开始,实验组大鼠后肢功能较对照组明显恢复(P<0.01),至第10周时,实验组和对照组BBB分差增大,达3.3分。结论Lentivirus是一种有效的转基因载体,由Lentivirus介导分泌NT-3的直接体内转基因治疗能够明显促进损伤脊髓的功能恢复。 | 蔡培强 汤逊 林月秋 Oudega Mart 徐林 Blits B 阳运康 M.OUDEGA | 2005 | 中华创伤杂志2005，21，7： | 2 |
| 8 | Neurotrophins reduce degeneration of injured ascending sensory and corticospinal motor axons in adult rat spinal cord显示文摘 | Sayer FT Oudega M Hagg T | 2002 | Exp Neurol2002，175，： | 1 |
| 9 | Axonal regeneration into Schwann cel grafts within resorbable poly(-alpha-hydroxyacid) guidance channels in the adult rat spinal cord显示文摘 | Oudega M Gautier SE Chapon P | | 0，，10： | 1 |
| 10 | Diagnostic classification in patients with suspected deep venous thrombosis: physicians' judgement or a decision rule显示文摘 | Geersing GJ Janssen K Oudega R | 2010 | Br J Gen Pract2010，60，： | 1 |
| 11 | Schwann cell transplantation for repair of the adult spinal cord显示文摘 | Oudega M Xu XM | | 0，，3： | 1 |
| 12 | Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care:retrospective,cross sectional,diagnostic analysis显示文摘 | Schouten HJ Koek HL Oudega R | | 0，，： | 1 |
| 13 | Schwann cellss for spinal cord repair显示文摘 | Oudega M Moon LD de Almeida Leme RJ | | 0，，06： | 1 |
| 14 | Schwann cell transplantation for repair of the adult spinal cord显示文摘 | Oudega M Xu XM | 2006 | J Neurotrauma2006，23，34： | 1 |
| 15 | Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord显示文摘 | Takami T Oudega M Bates ML | | 0，，15： | 1 |
| 16 | Injury-induced class 3 semaphorin expression in the rat spinal cord显示文摘 | De Winter F Oudega M Lankhorst A J | | 0，，01： | 1 |
| 17 | Schwann cell transplantation for repair of the adult spinal cord 显示文摘 | Oudega M Xu XM | 2006 | J Neurotrauma2006，23，： | 1 |
| 18 | Schwann cells for spinal cord repair显示文摘 | Oudega M Moon LD de Almeida Leme RJ | | 0，，06： | 1 |
| 19 | Schwann call but not olfac- tory ensheathing glia transplants improve hindlimb locomotor per- formance in the moderately contused adult rat thoracic spinal cord 显示文摘 | Takami T Oudega M Bates ML | 2002 | J Neurosci2002，22，15： | 1 |
| 20 | Degenerative and spontaneous regenerative processes after spinal cord injury显示文摘 | HAGG T OUDEGA M | 2006 | Neurotrauma2006，23，34： | 1 |
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