Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat

Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat
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DOI:
10.1016/j.expneurol.2005.05.004
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发表时间:
2006-05-01
影响因子:
5.3
通讯作者:
Kocsis, J. D.
Kocsis, J. D.
中科院分区:
医学2区
文献类型:
--
作者:
Honma, T.;Honmou, O.;Kocsis, J. D.

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骨髓细胞的静脉输注已在脑缺血和脊髓损伤的动物模型中显示出治疗效果。我们将人端粒酶基因(hTERT-MSCs)永生化的人间充质干细胞(SH2+、SH3+、CD34(-)和CD45(-))经静脉注射并转染eGFP或LacZ,在诱导短暂性大脑中动脉闭塞(MCAO)后12 h注入大鼠体内,以研究其潜在的治疗益处。损伤诱导后,hTERT-MSC在12 It时递送。病变大小进行了评估,使用磁共振成像和光谱,和组织学方法。使用Morris水迷宫和跑步机测试评估功能结果。静脉注射hTERT-MSCs可以减少病变体积,并且减少和功能改善的幅度与注射的细胞数量呈正相关。病灶大小的减少可以在体内用MRI和MRS评估,并与随后的脑组织学检查相关。这项工作表明,高度纯化的hTERT-MSCs减少脑梗死体积并改善功能结果。(c)2005年爱思唯尔公司All rights reserved.
Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal models of cerebral ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34(-), and CD45(-)) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 It after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce cerebral infarction volume and improve functional outcome. (c) 2005 Elsevier Inc. All rights reserved.