Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California 95817, USA.
Nat Commun. 2013;4:2196. doi: 10.1038/ncomms3196.
Human pluripotent stem cells (hPSCs) have been differentiated to astroglia, but the utilization of hPSC-derived astroglia as cell therapy for neurological diseases has not been well studied. Astroglia are heterogeneous, and not all astroglia are equivalent in promoting neural repair. A prerequisite for cell therapy is to derive defined cell populations with superior therapeutic effects. Here we use an Olig2-GFP human embryonic stem cell (hESC) reporter to demonstrate that hESC-derived Olig2(+) progenitors generate a subtype of previously uncharacterized astroglia (Olig2PC-Astros). These Olig2PC-Astros differ substantially from astroglia differentiated from Olig2-negative hESC-derived neural progenitor cells (NPC-Astros), particularly in their neuroprotective properties. When grafted into brains subjected to global ischaemia, Olig2PC-Astros exhibit superior neuroprotective effects and improved behavioural outcome compared to NPC-Astros. Thus, this new paradigm of human astroglial differentiation is useful for studying the heterogeneity of human astroglia, and the unique Olig2PC-Astros may constitute a new cell therapy for treating cerebral ischaemia and other neurological diseases.
人多能干细胞（hPSCs）已分化为星形胶质细胞，但 hPSC 衍生的星形胶质细胞作为神经疾病的细胞治疗尚未得到很好的研究。星形胶质细胞具有异质性，并非所有星形胶质细胞在促进神经修复方面都等效。细胞治疗的前提是衍生具有优越治疗效果的定义明确的细胞群体。在这里，我们使用 Olig2-GFP 人胚胎干细胞（hESC）报告基因来证明 hESC 衍生的 Olig2(+)祖细胞产生了一种以前未表征的星形胶质细胞（Olig2PC-Astros）亚型。这些 Olig2PC-Astros 与从 Olig2-阴性 hESC 衍生的神经祖细胞（NPC-Astros）分化而来的星形胶质细胞有很大不同，特别是在其神经保护特性方面。当移植到经历全脑缺血的大脑中时，与 NPC-Astros 相比，Olig2PC-Astros 表现出更好的神经保护作用和改善的行为结果。因此，这种新型的人类星形胶质细胞分化范例可用于研究人类星形胶质细胞的异质性，而独特的 Olig2PC-Astros 可能构成治疗脑缺血和其他神经疾病的新细胞治疗方法。
