BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model
BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model
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DOI：
10.1016/j.ymthe.2003.10.012
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发表时间：
2004-02-01
影响因子：
12.4
通讯作者：
Hamada, H
中科院分区：
文献类型：
--
作者：
Kurozumi, K;Nakamura, K;Hamada, H
使用骨髓基质细胞，包括间充质干细胞（MSC）的临床治疗效果的检查，最近已经成为许多研究的焦点。据报道，MSC可以改善大鼠中风后的功能缺陷，其中一些改善可能是由于这些细胞分泌的细胞因子的作用。为了增强这种细胞因子的作用，我们使用纤维突变型F/RGD腺病毒载体转染BDNF基因的端粒化人MSC，并研究这些细胞是否有助于改善大鼠短暂性大脑中动脉闭塞（MCAO）模型的功能恢复。由MSC-BDNF细胞产生的BDNF是未感染MSC中所见的BDNF的23倍。接受MSC-BDNF的大鼠在MCAO后的功能恢复明显优于对照组。具体来说，MRI分析显示，MSC-BDNF组的大鼠在7天和14天后表现出更显著的缺血恢复。与对照组动物相比，用MSC-BDNF治疗的动物中缺血边界区的TUNEL阳性细胞数量显著较少。这些数据表明，转染BDNF基因的MSC可能在治疗脑缺血方面是有用的，并可能代表治疗中风的新策略。
Examination of the clinical therapeutic efficacy of using bone marrow stromal cells, including mesenchymal stem cells (MSC), has recently been the focus of much investigation. MSC were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we transfected telomerized human MSC with the BDNF gene using a fiber-mutant F/RGD adenovirus vector and investigated whether these cells contributed to improved functional recovery in a rat transient middle cerebral artery occlusion (MCAO) model. BDNF production by MSC-BDNF cells was 23-fold greater than that seen in uninfected MSC. Rats that received MSC-BDNF showed significantly more functional recovery than did control rats following MCAO. Specifically, MRI analysis revealed that the rats in the MSC-BDNF group exhibited more significant recovery from ischemia after 7 and 14 days. The number of TUNEL-positive cells in the ischemic boundary zone was significantly smaller in animals treated with MSC-BDNF compared to animals in the control group. These data suggest that MSC transfected with the BDNF gene may be useful in the treatment of cerebral ischemia and may represent a new strategy for the treatment of stroke.