Zhang Su-Chun, Li Xue-Jun, Johnson M Austin, Pankratz Matthew T
Department of Anatomy and Neurology, School of Medicine and Public Health, Waisman Centre, WiCell Institute, University of Wisconsin, Madison, WI 53705, USA.
Philos Trans R Soc Lond B Biol Sci. 2008 Jan 12;363(1489):87-99. doi: 10.1098/rstb.2006.2014.
Cell therapy has been perceived as the main or ultimate goal of human embryonic stem (ES) cell research. Where are we now and how are we going to get there? There has been rapid success in devising in vitro protocols for differentiating human ES cells to neuroepithelial cells. Progress has also been made to guide these neural precursors further to more specialized neural cells such as spinal motor neurons and dopamine-producing neurons. However, some of the in vitro produced neuronal types such as dopamine neurons do not possess all the phenotypes of their in vivo counterparts, which may contribute to the limited success of these cells in repairing injured or diseased brain and spinal cord in animal models. Hence, efficient generation of neural subtypes with correct phenotypes remains a challenge, although major hurdles still lie ahead in applying the human ES cell-derived neural cells clinically. We propose that careful studies on neural differentiation from human ES cells may provide more immediate answers to clinically relevant problems, such as drug discovery, mechanisms of disease and stimulation of endogenous stem cells.
细胞疗法一直被视为人类胚胎干细胞(ES细胞)研究的主要或最终目标。我们目前处于什么阶段,又将如何实现这一目标呢?在设计将人类ES细胞分化为神经上皮细胞的体外方案方面已迅速取得成功。在进一步引导这些神经前体细胞分化为更特化的神经细胞,如脊髓运动神经元和产生多巴胺的神经元方面也取得了进展。然而,一些体外产生的神经元类型,如多巴胺神经元,并不具备其体内对应物的所有表型,这可能导致这些细胞在动物模型中修复受损或患病的脑和脊髓方面取得的成功有限。因此,高效生成具有正确表型的神经亚型仍然是一项挑战,尽管将人类ES细胞衍生的神经细胞应用于临床仍面临诸多重大障碍。我们认为,对人类ES细胞神经分化进行仔细研究可能会为临床相关问题,如药物发现、疾病机制和内源性干细胞的刺激,提供更直接的答案。