研究人員利用從人類胚胎提取的干細胞成功治愈小鼠和大鼠的帕金森氏癥,。對于為人類找到類似治療方法來說,，這是關(guān)鍵的一步。
本周日在科學期刊《自然》上發(fā)表的一項研究中,，科學家描述了他們將人類胚胎干細胞轉(zhuǎn)化為能夠產(chǎn)生大腦化學物質(zhì)多巴胺（dopamine）的神經(jīng)細胞的過程,。當這樣的神經(jīng)細胞被移植到大鼠和小鼠的大腦中后，這些細胞就能釋放多巴胺,，而大鼠和小鼠表現(xiàn)出的帕金森氏癥狀也隨之消失了,。這種神經(jīng)細胞也被成功地移植到了生物學特性與人類更接近的恒河猴（rhesus monkey）大腦中。
論文的第一作者施圖德（Lorenz Studer）說,，我們認為很有可能將這種方法發(fā)展真正的細胞療法,，治愈人類的疾病。現(xiàn)在我們面臨的更多的是工程上的問題,，而非科學上的障礙,。施圖德是紐約斯隆-凱特琳癌癥中心（Sloan-Kettering Institute for Cancer Research）的干細胞生物學家。
神經(jīng)細胞利用多巴胺輔助控制肌肉運動,。對于目前還沒有治愈方法的帕金森氏癥的患者來說,，大腦中產(chǎn)生多巴胺的細胞慢慢被破壞。這會影響大腦發(fā)送信息的能力,，從而導致肌肉功能的受損,、運動減少，并引發(fā)抖顫。目前有藥物能夠增加大腦中多巴胺的分泌量并控制帕金森氏癥狀,，但這些藥物能夠引發(fā)不自主運動等副作用,。而且隨著病情的加重，藥物的療效也會逐漸減弱,。
一些科學家正在進行細胞移植試驗。他們利用采自小鼠胚胎的干細胞轉(zhuǎn)化為能夠產(chǎn)生多巴胺的細胞,，用于治療患有帕金森氏癥的動物,。但在此之前，利用人類胚胎干細胞以類似方法治療小鼠并沒有取得理想的效果,。這不僅是因為源自人類的多巴胺細胞被移植到動物體內(nèi)后無法有效地發(fā)揮作用,，也因為這些細胞會引發(fā)腫瘤樣結(jié)構(gòu)的生長，而這是人們所不希望看到的,。(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.
