Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells

Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells
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DOI:
10.1016/j.ejcb.2005.09.021
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发表时间:
2006-01-01
影响因子:
6.6
通讯作者:
Wolf, G
Wolf, G
中科院分区:
生物学3区
文献类型:
--
作者:
Keilhoff, G;Goihl, A;Wolf, G

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骨髓基质细胞(MSC)是一种多能分化为中胚层细胞系的干细胞。虽然是成虫,但分化潜力显著,具有转分化能力。经转分化培养的大鼠间充质干细胞(tMSC)与未处理的大鼠间充质干细胞(rMSC)相比,在形态上改变为与典型纺锤形雪旺细胞(SC)相似的细胞,LNGF受体、Krox-20、CD104和S100 β蛋白的表达增强,骨形态发生蛋白受体- 1a的表达降低。转分化是可逆和可重复的。为了评估髓鞘形成能力,将雄性大鼠培养的rMSC、tMSC或SC移植到雌性大鼠坐骨神经2厘米间隙的自体肌管中。男性特异性SRY基因的存在(PCR分析显示)和预标记tMSC的s100免疫反应性证实移植物中存在植入细胞。移植后3周,SC组和tMSC组均有一定程度的再生,而rMSC组和未移植任何细胞的对照组再生均受损。与SC相反,在某些情况下,单个tMSC能够形成一个以上的轴突。我们的研究结果表明,将MSC分化为临床应用的治疗有用细胞是可能的。(c) 2005 Elsevier GmbH版权所有。
Bone marrow stromal cells (MSC) are multipotent stein cells that differentiate into cells of the mesodermal lineage. Although adult, their differentiation potential is remarkable, and they are able to transdifferentiate. Transdifferentiated cultivated rat MSC (tMSC) changed morphologically into cells resembling typical spindle-shaped Schwann cells (SC) with enhanced expression of LNGF receptor, Krox-20, CD104 and S100 beta protein and decreased expression of bone morphogenetic protein receptor-1A compared to untreated rat MSC (rMSC). Transdifferentiation was reversible and repeatable. To evaluate the myelinating capacity, rMSC, tMSC, or SC cultured from male rats were grafted into an autologous muscle conduit bridging a 2-cm gap in the female rat sciatic nerve. The presence of the male-specific SRY gene (as revealed by PCR analysis) and S 100 immunoreactivity of pre-labeled tMSC confirmed the presence of the implanted cells in the grafts. Three weeks after grafting, an appropriate regeneration was noted in the SC and in the tMSC groups, while regeneration in the rMSC group and in the control group without any cells was impaired. In contrast to SC, in some cases, single tMSC were able to myelinate more than one axon. Our findings demonstrate that it may be possible to differentiate MSC into therapeutically useful cells for clinical applications. (c) 2005 Elsevier GmbH. All rights reserved.