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首页> 外文期刊>Neurosurgery >Umbilical cord-derived mesenchymal stem cells with forced expression of hepatocyte growth factor enhance remyelination and functional recovery in a rat intracerebral hemorrhage model.
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Umbilical cord-derived mesenchymal stem cells with forced expression of hepatocyte growth factor enhance remyelination and functional recovery in a rat intracerebral hemorrhage model.

机译:在大鼠脑出血模型中,脐带来源的间充质干细胞具有强制性肝细胞生长因子的表达,可增强髓鞘再生和功能恢复。

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BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) carries a high mortality rate, with survivors commonly left with permanent neurological deficits. Mesenchymal stem cell (MSC) transplantation promotes functional recovery in experimental ICH, and treatment with hepatocyte growth factor (HGF) is beneficial in ischemic stroke. OBJECTIVE: We hypothesize that transplantation of MSCs with previous transduction of HGF has an additive effect in promoting neurological recovery through myelin and axonal regeneration. METHODS: HGF transduction to human umbilical cord-derived MSCs using lentiviral plasmid pWPI-HGF-GFP was prepared. One week after a collagenase-induced ICH, 80 male Sprague-Dawley rats were divided into 3 groups for stereotactic injection of phosphate-buffered saline (group I), MSC transplant (group II), and HGF-transduced MSC transplant (group III), respectively, into the left ventricle. The animals were assessed weekly for 5 weeks using the Rotarod motor function test, at which time they were killed for Luxol fast blue myelin staining and appropriate immunohistochemistry and Western blotting. RESULTS: Animals receiving transplanted HGF-transduced MSCs (group III) exhibited significantly better motor function recovery than animals treated with MSCs alone (group II), which in turn performed better than the phosphate-buffered saline controls at 2 weeks after transplantation. Luxol fast blue staining of myelin displayed significantly less demyelination and significantly higher reactivity in myelin basic protein and growth-associated protein-43 in immunohistochemistry and Western blotting and significantly reduced myelin-associated glycoprotein activity in group III animals. CONCLUSION: Animals transplanted with HGF-transduced MSCs 1 week after experimental ICH were shown to achieve a better neurological recovery. This improved neurological recovery from ICH is attributed to nerve fiber remyelination and axonal regeneration.
机译:背景:自发性脑出血(ICH)的死亡率很高,幸存者通常患有永久性神经功能缺损。间充质干细胞(MSC)移植促进实验性ICH的功能恢复,而肝细胞生长因子(HGF)的治疗对缺血性卒中有益。目的:我们假设MSCs先行HGF的转导具有通过髓鞘和轴突再生促进神经恢复的附加作用。方法:利用慢病毒质粒pWPI-HGF-GFP制备HGF转导人脐带间充质干细胞。胶原酶诱导的ICH后一周,将80只雄性Sprague-Dawley大鼠分为3组,分别进行立体定向注射磷酸盐缓冲液(I组),MSC移植(II组)和HGF转导的MSC移植(III组)分别进入左心室。使用Rotarod运动功能测试每周评估动物5周,然后将其杀死以进行Luxol固蓝髓磷脂染色以及适当的免疫组化和Western印迹。结果:与单独用MSCs治疗的动物(II组)相比,接受HGF转导的MSCs的动物(III组)表现出明显更好的运动功能恢复,而在移植2周后,它们的表现优于磷酸盐缓冲液。在免疫组化和Western印迹中,髓鞘的Luxol固蓝染色显示髓鞘碱性蛋白和生长相关蛋白43的脱髓鞘明显减少,反应性显着更高,并且在III组动物中显着降低了髓鞘相关糖蛋白的活性。结论:实验性ICH后1周移植了HGF转导的MSC的动物显示出更好的神经恢复。从ICH改善的神经功能恢复归因于神经纤维的髓鞘再生和轴突再生。

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