Behavioral and histological evaluation of a focal cerebral infarction rat model transplanted with neurons induced from bone marrow stromal cells
Behavioral and histological evaluation of a focal cerebral infarction rat model transplanted with neurons induced from bone marrow stromal cells
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DOI：
10.1097/01.jnen.0000190068.03009.b5
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发表时间：
2005-12-01
影响因子：
3.2
通讯作者：
Yamamoto, I
中科院分区：
文献类型：
--
作者：
Mimura, T;Dezawa, M;Yamamoto, I
利用Notch胞内区的基因转移和碱性成纤维细胞生长因子、Forsklin和睫状神经营养因子的处理，可以极高效率地从骨髓基质细胞(MSCs)特异性地诱导出神经元。我们研究了这种骨髓基质细胞衍生的神经元细胞(MSDNC)移植到大鼠局灶性脑梗塞模型中的行为和组织学效果。成年Wistar大鼠左侧大脑中动脉闭塞(MCAO)。于MCAO后第7天将MSDNC移植至同侧大脑半球。在第14、21、28、35和36-40天进行行为分析，并在第41天进行组织学评估。移植MSDNC的大鼠在平衡木平衡、肢体放置和Morris水迷宫测试中与对照组(未进行细胞移植的MCAO)相比显著恢复。组织学上，移植细胞从注射部位迁移到缺血边界区域，包括皮质、胼胝体、纹状体和海马体。移植的MSDNCs MAP-2阳性细胞占84%(+/-8.11%)，而GFAP阳性细胞仅占少数(1.0%+/-0.23%)。移植后1个月，MSDNCs和MSCs的存活率分别约为45%和10%。这些结果表明，应用MSDNCs可能是治疗脑梗塞的一种有前途的策略。
Neurons can be specifically induced from bone marrow stromal cells (MSCs) with extremely high efficiency using gene transfection of the Notch intracellular domain and subsequent treatment with basic-fibroblast growth factor, forskolin, and ciliary neurotrophic factor. We investigated the behavioral and histologic efficacy of such bone marrow stromal cell-derived neuronal cell (MSDNC) transplantation into a focal cerebral infarction model in rats. A left middle cerebral artery occlusion (MCAO) was performed on adult Wistar rats. MSDNC transplantation into the ipsilateral hemisphere was performed on day 7 after MCAO. The behavioral analyses were conducted on days 14, 21, 28, 35, and 36-40, and a histologic evaluation was performed on day 41. MSDNC-transplanted rats showed significant recovery compared with controls (MCAO without cell transplantation) in beam balance, limb placing, and Morris water maze tests. Histologically, transplanted cells migrated from the injection site into the ischemic boundary area, including the cortex, corpus callosum, striatum, and hippocampus. Transplanted MSDNCs were positive for MAP-2 (84% +/- 8.11 %), whereas only a small number of cells were positive for GFAP (1.0% +/- 0.23%). The survival rates of MSDNCs and MSCs 1 month after transplantation were approximately 45% and 10%, respectively. These results suggest that use of MSDNCs may be a promising therapeutic strategy for cerebral infarction.