研究人员利用从人类胚胎提取的干细胞成功治愈小鼠和大鼠的帕金森氏症。对于为人类找到类似治疗方法来说，这是关键的一步。
本周日在科学期刊《自然》上发表的一项研究中，科学家描述了他们将人类胚胎干细胞转化为能够产生大脑化学物质多巴胺（dopamine）的神经细胞的过程。当这样的神经细胞被移植到大鼠和小鼠的大脑中后，这些细胞就能释放多巴胺，而大鼠和小鼠表现出的帕金森氏症状也随之消失了。这种神经细胞也被成功地移植到了生物学特性与人类更接近的恒河猴（rhesus monkey）大脑中。
论文的第一作者施图德（Lorenz Studer）说，我们认为很有可能将这种方法发展真正的细胞疗法，治愈人类的疾病。现在我们面临的更多的是工程上的问题，而非科学上的障碍。施图德是纽约斯隆-凯特琳癌症中心（Sloan-Kettering Institute for Cancer Research）的干细胞生物学家。
神经细胞利用多巴胺辅助控制肌肉运动。对于目前还没有治愈方法的帕金森氏症的患者来说，大脑中产生多巴胺的细胞慢慢被破坏。这会影响大脑发送信息的能力，从而导致肌肉功能的受损、运动减少，并引发抖颤。目前有药物能够增加大脑中多巴胺的分泌量并控制帕金森氏症状，但这些药物能够引发不自主运动等副作用。而且随着病情的加重，药物的疗效也会逐渐减弱。
一些科学家正在进行细胞移植试验。他们利用采自小鼠胚胎的干细胞转化为能够产生多巴胺的细胞，用于治疗患有帕金森氏症的动物。但在此之前，利用人类胚胎干细胞以类似方法治疗小鼠并没有取得理想的效果。这不仅是因为源自人类的多巴胺细胞被移植到动物体内后无法有效地发挥作用，也因为这些细胞会引发肿瘤样结构的生长，而这是人们所不希望看到的。(生物谷 Bioon.com)
doi:10.1038/nature10648
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Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease
Sonja Kriks, Jae-Won Shim, Jinghua Piao, Yosif M. Ganat, Dustin R. Wakeman, Zhong Xie, Luis Carrillo-Reid, Gordon Auyeung, Chris Antonacci, Amanda Buch, Lichuan Yang, M. Flint Beal, D. James Surmeier, Jeffrey H. Kordower, Viviane Tabar & Lorenz Studer
Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However, the effective use of PSCs for cell therapy has lagged behind. Whereas mouse PSC-derived DA neurons have shown efficacy in models of Parkinson’s disease, DA neurons from human PSCs generally show poor in vivo performance. There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor-plate precursors are derived from PSCs 11 days after exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signalling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of PSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in Parkinson’s disease models using three host species. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson’s disease.
