Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation.
Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation.
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DOI：
10.1172/jci20935
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发表时间：
2004-06
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通讯作者：
M. Dezawa;H. Kanno;M. Hoshino;Hirotomi Cho;N. Matsumoto;Yutaka Itokazu;Nobuyoshi Tajima;Hitoshi Yamada-Hi
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文献类型：
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作者：
M. Dezawa;H. Kanno;M. Hoshino;Hirotomi Cho;N. Matsumoto;Yutaka Itokazu;Nobuyoshi Tajima;Hitoshi Yamada-Hi
骨髓基质细胞（MSCs）在特定条件下具有分化成各种细胞类型的能力，如骨细胞、软骨细胞和脂肪细胞。在这里，我们证明了一个高效和特异性的诱导细胞与神经元的特性，没有神经胶质细胞分化，从大鼠和人骨髓间充质干细胞使用基因转染与Notch细胞内结构域（NICD）和随后的治疗与bFGF，毛喉素，睫状神经营养因子。骨髓间充质干细胞表达神经干细胞相关的标记物与NICD转染后，和随后的营养因子管理诱导神经元细胞。其中一些显示电压门控快钠和延迟整流钾电流和动作电位与功能神经元的特征兼容。进一步用胶质细胞源性神经营养因子（GDNF）处理诱导的神经元细胞，增加酪氨酸羟化酶阳性和多巴胺产生细胞的比例。这些GDNF处理的细胞移植显示，在6-羟基多巴胺帕金森病大鼠模型纹状体内植入后，阿扑吗啡诱导的旋转行为和调整步骤和爪到达测试得到改善。这项研究表明，一个群体的神经元细胞可以特异性地产生从骨髓间充质干细胞和诱导细胞可能允许神经重建的方法。
Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line-derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase-positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.