Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model
Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model
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DOI：
10.1016/j.ymthe.2004.09.020
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发表时间：
2005-01-01
影响因子：
12.4
通讯作者：
Hamada, H
中科院分区：
文献类型：
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作者：
Kurozumi, K;Nakamura, K;Hamada, H
据报道，间充质干细胞（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，我们以前转染端粒的人骨髓间充质干细胞与BDNF基因的纤维突变腺病毒载体，并报告说，这种治疗有助于改善缺血恢复大鼠短暂性大脑中动脉闭塞（MCAO）模型。在本研究中，我们研究了除BDNF外的其他细胞因子，即，GDNF、CNTF或NT 3在该模型中可能具有类似或更大的作用。在MCAO后7天和14天，接受MSC-BDNF（P < 0.05）或MSC-GDNF（P < 0.05）的大鼠表现出明显更多的功能恢复，表现为行为测试结果的改善和MRI上缺血性损伤的减少。另一方面，与对照组大鼠相比，接受MSC-CNTF或MSC-NT 3的大鼠既没有功能恢复，也没有缺血性损伤减轻。因此，在MCAO大鼠模型中，转染BDNF或GDNF基因的MSC导致功能改善和缺血性损伤减少。这些数据表明，基因修饰的细胞疗法可能是治疗中风的一种有用的方法。
Mesenchymal stem cells (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 previously transfected the telomerized human MSC with the BDNF gene using a fiber-mutant adenovirus vector and reported that such treatment contributed to improved ischemic recovery in a rat transient middle cerebral artery occlusion (MCAO) model. In the present study, we investigated whether other cytokines in addition to BDNF, i.e., GDNF, CNTF, or NT3, might have a similar or greater effect in this model. Rats that received MSC-BDNF (P < 0.05) or MSC-GDNF (P < 0.05) showed significantly more functional recovery as demonstrated by improved behavioral test results and reduced ischemic damage on MRI than did control rats 7 and 14 days following MCAO. On the other hand, rats that received MSC-CNTF or MSC-NT3 showed neither functional recovery nor ischemic damage reduction compared to control rats. Thus, MSC transfected with the BDNF or GDNF gene resulted in improved function and reduced ischemic damage in a rat model of MCAO. These data suggest that gene-modified cell therapy may be a useful approach for the treatment of stroke.