Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: Effect of in vitro differentiation on graft survival and teratoma formation
Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: Effect of in vitro differentiation on graft survival and teratoma formation
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DOI：
10.1634/stemcells.2005-0393
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发表时间：
2006-06-01
期刊：
影响因子：
5.2
通讯作者：
Li, Jia-Yi
中科院分区：
文献类型：
--
作者：
Brederlau, Anke;Correia, Ana Sofia;Li, Jia-Yi
人类胚胎干细胞（hESCs）被认为是帕金森病（PD）移植中多巴胺（DA）神经元的来源。我们研究了体外预分化对植入6-OHDA（6-羟多巴胺）损伤大鼠PD模型的hESCs体内存活和分化的影响。hESCs与PA6细胞共培养16、20、23天，体外分化为DA神经元。移植的hesc来源的细胞存活良好，并表达神经元标记物。然而，很少表现出DA神经元表型。未观察到病变引起的运动缺陷的逆转。体外预分化hESCs移植16天的大鼠出现了严重的畸胎瘤，而移植20天和23天的大部分大鼠一直保持健康直到实验结束。这表明hESCs的体外长时间分化对于防止畸胎瘤的形成至关重要。
Human embryonic stem cells (hESCs) have been proposed as a source of dopamine (DA) neurons for transplantation in Parkinson's disease (PD). We have investigated the effect of in vitro predifferentiation on in vivo survival and differentiation of hESCs implanted into the 6-OHDA (6-hydroxydopamine)-lesion rat model of PD. The hESCs were cocultured with PA6 cells for 16, 20, or 23 days, leading to the in vitro differentiation into DA neurons. Grafted hESC-derived cells survived well and expressed neuronal markers. However, very few exhibited a DA neuron phenotype. Reversal of lesion-induced motor deficits was not observed. Rats grafted with hESCs predifferentiated in vitro for 16 days developed severe teratomas, whereas most rats grafted with hESCs predifferentiated for 20 and 23 days remained healthy until the end of the experiment. This indicates that prolonged in vitro differentiation of hESCs is essential for preventing formation of teratomas.