Brederlau Anke, Correia Ana Sofia, Anisimov Sergey V, Elmi Muna, Paul Gesine, Roybon Laurent, Morizane Asuka, Bergquist Filip, Riebe Ilse, Nannmark Ulf, Carta Manolo, Hanse Erik, Takahashi Jun, Sasai Yoshiki, Funa Keiko, Brundin Patrick, Eriksson Peter S, Li Jia-Yi
Institute of Anatomy and Cell Biology, Göteborg University, Gothenburg, Sweden.
Stem Cells. 2006 Jun;24(6):1433-40. doi: 10.1634/stemcells.2005-0393. Epub 2006 Mar 23.
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.
人类胚胎干细胞（hESCs）已被提议作为多巴胺（DA）神经元的来源，用于帕金森病（PD）的移植治疗。我们研究了体外预分化对植入6-羟基多巴胺（6-OHDA）损伤的PD大鼠模型体内hESCs存活和分化的影响。将hESCs与PA6细胞共培养16、20或23天，使其在体外分化为DA神经元。移植的hESC来源细胞存活良好并表达神经元标志物。然而，很少有细胞表现出DA神经元表型。未观察到损伤诱导的运动缺陷得到逆转。移植体外预分化16天的hESCs的大鼠发生了严重的畸胎瘤，而移植体外预分化20天和23天的hESCs的大多数大鼠在实验结束时仍保持健康。这表明hESCs的长时间体外分化对于预防畸胎瘤的形成至关重要。
