Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke
Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke
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DOI：
10.1038/jcbfm.2009.62
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发表时间：
2009-08-01
影响因子：
6.3
通讯作者：
Dezawa, Mari
中科院分区：
文献类型：
--
作者：
Hayase, Makoto;Kitada, Masaaki;Dezawa, Mari
骨髓基质细胞(MSCs)是治疗多种中枢神经系统疾病的良好细胞来源。在这项研究中，我们报道了通过导入含有Notch-1胞内域的细胞并在自由培养系统中生长来有效地诱导大鼠和人MSCs(NS-MSCs)定向神经前体细胞。NS-MSCs成功构建了球体，在球体中细胞高表达神经前体细胞标志物。当球体暴露在分化介质中时，它们成功地分化为神经细胞，证实了球体对神经系细胞的承诺。为了确定NS-MSCs的治疗潜力，在大鼠局灶性脑缺血模型中，将细胞移植到皮质和纹状体。移植的NS-MSCs在宿主脑内的存活率、分布和整合率都很高，在第100天，移植的NS-MSCs的多巴胺能、谷氨酸能和γ-氨基丁酸(GABA)能神经元标记呈阳性。它们将长神经突起延长近6.3毫米，其中许多表达突触素。在肢体放置和水迷宫测试中也观察到显著的行为恢复。这些都表明，这种MSC方法在中风和需要不同类型神经细胞的广泛神经退行性疾病的神经细胞补充方面具有很高的潜力。《脑血流与代谢杂志》(2009年)29期，1409-1420期；doi：10.1038/jcbfm.2009.62；2009年5月13日在线出版
Bone marrow stromal cells (MSCs) are an excellent source of cells for treating a variety of central nervous system diseases. In this study, we report the efficient induction of committed neural progenitor cells from rat and human MSCs (NS-MSCs) by introduction of cells with the intracellular domain of Notch-1 followed by growth in the free-floating culture system. NS-MSCs successfully formed spheres, in which cells highly expressed the neural precursor cell markers. The commitment of spheres to neural lineage cells was confirmed by their successful differentiation into neuronal cells when exposed to a differentiation medium. To determine the therapeutic potential of NS-MSCs, cells were transplanted into the cortex and striatum in a rat model of focal cerebral ischemia. The survival, distribution, and integration of NS-MSCs in the host brain were very high, and at day 100, grafted NS-MSCs were positive for dopaminergic, glutamatergic, and gamma-amino butyric acid (GABA)ergic neuronal markers. They extended long neurites for nearly 6.3 mm and many of these expressed synaptophysin. Significant behavioral recovery was also observed in limb-placing and water-maze tests. These suggest a high potential for this MSC approach in the replenishment of neural cells for stroke and for a wide range of neurodegenerative conditions that require various types of neural cells. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1409-1420; doi: 10.1038/jcbfm.2009.62; published online 13 May 2009