Adult rat and human bone marrow stromal cells differentiate into neurons

Adult rat and human bone marrow stromal cells differentiate into neurons
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DOI:
10.1002/1097-4547(20000815)61:4
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发表时间:
2000-08
影响因子:
4.2
通讯作者:
D. Woodbury;E. Schwarz;D. Prockop;I. Black
D. Woodbury;E. Schwarz;D. Prockop;I. Black
中科院分区:
医学3区
文献类型:
--
作者:
D. Woodbury;E. Schwarz;D. Prockop;I. Black

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骨髓基质细胞表现出干细胞群体的多种特征。它们可以在体外大量扩增,并被诱导分化为多种类型的间充质细胞。然而,分化为非间充质细胞的命运尚未被证实。在这里,成年大鼠的基质细胞作为未分化的细胞在培养中扩增了20多代,表明其具有增殖能力。一种简单的治疗方案诱导基质细胞呈现神经元表型,表达神经元特异性烯醇化酶、NeuN、神经丝蛋白-M和tau。在最佳分化方案下,近80%的细胞表达NSE和NF-M。折射细胞体延长长的突起,终止于典型的生长锥体和丝状足基。分化细胞在5小时后表达巢蛋白,这是神经前体干细胞的特征,但在6天时检测不到这种特征。相反,神经生长因子受体TrkA的表达从5小时持续到6天。从单个细胞建立的克隆细胞系可以增殖,产生未分化的细胞和神经细胞。遵循这一方案的人骨髓基质细胞也会分化为神经元。因此,成人骨髓基质细胞可以被诱导为克服其间充质干细胞的承诺,并可能构成一个丰富的和可获得的细胞库,用于治疗各种神经疾病。J.神经学2000年,结果61:364-370。©2000 Wiley-Liss Inc.
Bone marrow stromal cells exhibit multiple traits of a stem cell population. They can be greatly expanded in vitro and induced to differentiate into multiple mesenchymal cell types. However, differentiation to non‐mesenchymal fates has not been demonstrated. Here, adult rat stromal cells were expanded as undifferentiated cells in culture for more than 20 passages, indicating their proliferative capacity. A simple treatment protocol induced the stromal cells to exhibit a neuronal phenotype, expressing neuron‐specific enolase, NeuN, neurofilament‐M, and tau. With an optimal differentiation protocol, almost 80% of the cells expressed NSE and NF‐M. The refractile cell bodies extended long processes terminating in typical growth cones and filopodia. The differentiating cells expressed nestin, characteristic of neuronal precursor stem cells, at 5 hr, but the trait was undetectable at 6 days. In contrast, expression of trkA, the nerve growth factor receptor, persisted from 5 hr through 6 days. Clonal cell lines, established from single cells, proliferated, yielding both undifferentiated and neuronal cells. Human marrow stromal cells subjected to this protocol also differentiated into neurons. Consequently, adult marrow stromal cells can be induced to overcome their mesenchymal commitment and may constitute an abundant and accessible cellular reservoir for the treatment of a variety of neurologic diseases. J. Neurosci. Res. 61:364–370, 2000. © 2000 Wiley‐Liss, Inc.