Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke.
Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke.
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DOI：
10.1186/scrt159
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发表时间：
2013-01-28
影响因子：
7.5
通讯作者：
Díez-Tejedor E
中科院分区：
文献类型：
--
作者：
Gutiérrez-Fernández M;Rodríguez-Frutos B;Ramos-Cejudo J;Teresa Vallejo-Cremades M;Fuentes B;Cerdán S;Díez-Tejedor E
干细胞治疗可以促进中风的良好恢复。多项研究表明，间充质干细胞（MSC）是安全有效的。然而，需要从动物模型中获得更多关于适当细胞类型的信息。本研究旨在分析急性静脉（i. v.）施用同种异体骨髓-（BM-MSC）和脂肪来源的干细胞（AD-MSC）对功能评价结果和脑修复标志物的影响。在大鼠永久性大脑中动脉闭塞（pMCAO）后30分钟静脉注射同种异体MSC（2 × 106个细胞）。通过磁共振成像（MRI）和免疫组化分析肿瘤体积和细胞迁移和植入。通过Rogers和旋转棒试验评价功能，并测定细胞增殖和细胞死亡。通过共聚焦显微镜分析脑修复标记物，并通过蛋白质印迹法证实。与梗死组相比，静脉注射BM-MSC或AD-MSC后24 h功能明显改善，14 d功能仍持续改善。未观察到梗死体积减少或细胞向受损脑中的任何迁移/植入。然而，相对于梗死组，两个治疗组中细胞死亡减少，细胞增殖显著增加。注射MSC后14 d，血管内皮生长因子（VEGF）、突触素（SYP）、少突胶质细胞（Olig-2）和神经丝蛋白（NF）水平显著升高，胶质纤维酸性蛋白（GFAP）水平显著降低。在pMCAO梗塞中静脉内施用同种异体MSC --无论是BM-MSC还是AD-MSC--与梗塞后14天的良好功能恢复、细胞死亡减少以及细胞增殖、神经发生、少突细胞发生、突触发生和血管生成标记物增加相关。
Stem cell therapy can promote good recovery from stroke. Several studies have demonstrated that mesenchymal stem cells (MSC) are safe and effective. However, more information regarding appropriate cell type is needed from animal model. This study was targeted at analyzing the effects in ischemic stroke of acute intravenous (i.v.) administration of allogenic bone marrow- (BM-MSC) and adipose-derived-stem cells (AD-MSC) on functional evaluation results and brain repair markers. Allogenic MSC (2 × 106 cells) were administered intravenously 30 minutes after permanent middle cerebral artery occlusion (pMCAO) to rats. Infarct volume and cell migration and implantation were analyzed by magnetic resonance imaging (MRI) and immunohistochemistry. Function was evaluated by the Rogers and rotarod tests, and cell proliferation and cell-death were also determined. Brain repair markers were analyzed by confocal microscopy and confirmed by western blot. Compared to infarct group, function had significantly improved at 24 h and continued at 14 d after i.v. administration of either BM-MSC or AD-MSC. No reduction in infarct volume or any migration/implantation of cells into the damaged brain were observed. Nevertheless, cell death was reduced and cellular proliferation significantly increased in both treatment groups with respect to the infarct group. At 14 d after MSC administration vascular endothelial growth factor (VEGF), synaptophysin (SYP), oligodendrocyte (Olig-2) and neurofilament (NF) levels were significantly increased while those of glial fiibrillary acid protein (GFAP) were decreased. i.v. administration of allogenic MSC - whether BM-MSC or AD-MSC, in pMCAO infarct was associated with good functional recovery, and reductions in cell death as well as increases in cellular proliferation, neurogenesis, oligodendrogenesis, synaptogenesis and angiogenesis markers at 14 days post-infarct.