Intravenous administration of glial cell line-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in the adult rat
Intravenous administration of glial cell line-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in the adult rat
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DOI：
10.1002/jnr.21056
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发表时间：
2006-11-15
影响因子：
4.2
通讯作者：
Kocsis, Jeffery D.
中科院分区：
文献类型：
--
作者：
Horita, Yoshifumi;Honmou, Osamu;Kocsis, Jeffery D.
据报道，静脉注射成人骨髓制备的人间充质干细胞（hMSCs）可以改善大鼠脑动脉闭塞后的功能缺陷。人们提出了几种假说来解释这些治疗效果，目前的想法是神经保护而不是神经发生起作用。为了潜在地提高hMSCs的治疗效果，我们使用纤维突变型F/RGD腺病毒载体转染了胶质细胞系来源的神经营养因子（GDNF）基因，并研究了GDNF基因修饰的hMSCs （GDNF-hMSCs）是否有助于大鼠永久性大脑中动脉闭塞（MCAO）模型的功能恢复。我们采用腔内血管闭塞法诱导MCAO， 3小时后静脉注入GDNF-hMSCs。MRI和行为学分析显示，与对照组相比，接受GDNF-hMSC或hMSCs的大鼠缺血恢复能力增强，但GDNF-hMSC组的效果更大。因此，这些结果表明，使用纤维突变腺病毒载体静脉给药转染GDNF基因的hMSCs可能对脑缺血有用，并可能代表一种治疗中风的新策略。(c) 2006 Wiley-Liss, Inc。
Intravenous administration of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Several hypotheses to account for these therapeutic effects have been suggested, and current thinking is that neuroprotection rather than neurogenesis is responsible. To enhance the therapeutic benefits of hMSCs potentially, we transfected hMSCs with the glial cell line-derived neurotrophic factor (GDNF) gene using a fiber-mutant F/RGD adenovirus vector and investigated whether GDNF gene-modified hMSCs (GDNF-hMSCs) could contribute to functional recovery in a rat permanent middle cerebral artery occlusion (MCAO) model. We induced MCAO by using intraluminal vascular occlusion, and GDNF-hMSCs were intravenously infused into the rats 3 hr later. MRI and behavioral analyses revealed that rats receiving GDNF-hMSCs or hMSCs exhibited increased recovery from ischemia compared with the control group, but the effect was greater in the GDNF-hMSC group. Thus, these results suggest that intravenous administration of hMSCs transfected with the GDNF gene using a fiber-mutant adenovirus vector may be useful in the cerebral ischemia and may represent a new strategy for the treatment of stroke. (c) 2006 Wiley-Liss, Inc.