Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurological outcome after transient focal cerebral ischemia in rats
Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurological outcome after transient focal cerebral ischemia in rats
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DOI：
10.1161/01.str.0000190006.88896.d3
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发表时间：
2005-12-01
期刊：
影响因子：
8.3
通讯作者：
Miyatake, SI
中科院分区：
文献类型：
--
作者：
Ikeda, N;Nonoguchi, N;Miyatake, SI
背景和目的：成纤维细胞生长因子-2（FGF-2）和骨髓基质细胞（MSC）移植可以改善闭塞性脑血管病后的神经功能缺损。在本研究中，我们研究了短暂性大脑中动脉闭塞（MCAO）后，大鼠神经功能改善的影响，通过一种新的治疗策略与FGF-2基因转移间充质干细胞的单纯疱疹病毒1型（HSV-1）vector.Methods -成年Wistar大鼠麻醉。在短暂性右侧MCAO后24小时，脑内施用未修饰的MSC、用HSV-11764/-4/pR19/ssIL 2-FGF-2修饰的MSC或PBS。所有动物进行21天的行为学测试，并在MCAO后3天和14天用2-3-5-三苯基四唑检测梗死体积。在MCAO后3天和7天，用ELISA测量MCAO同侧半球中的FGF-2产生。7和14天后的MCAO，免疫组化染色FGF-2applied.Results -中风动物接受FGF-2修饰的MSC表现出显着的功能恢复与其他组相比。MCAO后14天，仅FGF-2修饰的MSC治疗组的梗死体积显著减少。在MCAO后第3天和第7天，FGF-2修饰的MSC处理的脑中FGF-2的产生显著高于其他组。管理FGF-2修饰的MSC强烈表达FGF-2蛋白，这是由ELISA.Conclusions证明-我们的数据表明，FGF-2基因修饰的MSC与HSV-1载体可以有助于显着的功能恢复后，中风相比，单独的MSC移植。
Background and Purpose - Fibroblast growth factor-2 (FGF-2) administration and bone marrow stromal cell ( MSC) transplantation could improve neurological deficits after occlusive cerebrovascular disease. In the present study, we examined the effects of neurological improvement after transient middle cerebral artery occlusion (MCAO) in rats by a novel therapeutic strategy with FGF-2 gene-transferred MSCs by the herpes simplex virus type 1 (HSV-1) vector.Methods - Adult Wistar rats were anesthetized. Nonmodified MSCs, FGF-2- modified MSCs with HSV-1 1764/-4/pR19/ ssIL2-FGF-2, or PBS was administered intracerebrally 24 hours after transient right MCAO. All animals underwent behavioral tests for 21 days, and the infarction volume with 2-3-5-triphenylterazolium was detected 3 days and 14 days after the MCAO. Three days and 7 days after the MCAO, the FGF-2 production in the ipsilateral hemisphere of the MCAO was measured with ELISA. Seven and 14 days after the MCAO, immunohistochemical staining for FGF-2 was applied.Results - The stroke animals receiving FGF-2-modified MSCs demonstrated significant functional recovery compared with the other groups. Fourteen days after the MCAO, there was a significant reduction in infarction volume only in FGF-2-modified MSC-treated group. FGF-2 production in the FGF-2-modified MSC-treated brain was significantly higher compared with the other groups at 3 and 7 days after MCAO. Administrated FGF-2-modified MSCs strongly expressed the FGF-2 protein, which was proven by ELISA.Conclusions - Our data suggest that the FGF-2 gene-modified MSCs with the HSV-1 vector can contribute to remarkable functional recovery after stroke compared with MSCs transplantation alone.