Generation of neural stem cell-like cells from bone marrow-derived human mesenchymal stem cells.

Generation of neural stem cell-like cells from bone marrow-derived human mesenchymal stem cells.
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从骨髓来源的人间充质干细胞产生神经干细胞样细胞。

DOI:
10.1179/1743132811y.0000000053
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发表时间:
2011-12
影响因子:
1.9
通讯作者:
Qu T
Qu T
中科院分区:
医学4区
文献类型:
--
作者:
Ma K;Fox L;Shi G;Shen J;Liu Q;Pappas JD;Cheng J;Qu T

文献摘要

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在适当的培养条件下,骨髓(BM)来源的间充质干细胞能够分化成与其表型胚胎起源无关的多种细胞类型,包括神经细胞。在这里,我们报告了从骨髓来源的人间充质干细胞(hMSC)成功生成神经干细胞(NSC)样细胞。最初,hMSC 在人神经干细胞的条件培养基中培养。在该培养系统中,hMSC 被诱导成为 NSC 样细胞,在神经球样结构中增殖并表达早期 NSC 标记。与中枢神经系统来源的 NSC 一样,这些骨髓来源的 NSC 样细胞能够分化为表达神经元、星形胶质细胞和少突胶质细胞的神经标记物的细胞。全细胞膜片钳记录显示,与 NSC 样细胞分化的神经元样细胞表现出神经元的电生理特性,包括动作电位。将类 NSC 细胞移植到小鼠大脑中,证实这些类 NSC 细胞在体内保留了分化为神经元和神经胶质细胞的能力。我们的数据表明,多能 NSC 样细胞可以从培养的骨髓来源的 hMSC 中有效产生,并且这些细胞可以作为人类神经干细胞的有用替代品,用于潜在的临床应用,例如自体神经替代疗法。
Under appropriate culture conditions, bone marrow (BM)-derived mesenchymal stem cells are capable of differentiating into diverse cell types unrelated to their phenotypical embryonic origin, including neural cells. Here, we report the successful generation of neural stem cell (NSC)-like cells from BM-derived human mesenchymal stem cells (hMSCs). Initially, hMSCs were cultivated in a conditioned medium of human neural stem cells. In this culture system, hMSCs were induced to become NSC-like cells, which proliferate in neurosphere-like structures and express early NSC markers. Like central nervous system-derived NSCs, these BM-derived NSC-like cells were able to differentiate into cells expressing neural markers for neurons, astrocytes, and oligodendrocytes. Whole-cell patch clamp recording revealed that neuron-like cells, differentiated from NSC-like cells, exhibited electrophysiological properties of neurons, including action potentials. Transplantation of NSC-like cells into mouse brain confirmed that these NSC-like cells retained their capability to differentiate into neuronal and glial cells in vivo. Our data show that multipotent NSC-like cells can be efficiently produced from BM-derived hMSCs in culture and that these cells may serve as a useful alternative to human neural stem cells for potential clinical applications such as autologous neuroreplacement therapies.