hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury

Peng Jiang, Chen Chen, Ruimin Wang, Olga V. Chechneva, Seung-Hyuk Chung, Mahendra S. Rao, David E. Pleasure, Ying Liu, Quanguang Zhang and Wenbin Deng ()
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Peng Jiang: School of Medicine, University of California
Chen Chen: School of Medicine, University of California
Ruimin Wang: Institute of Molecular Medicine and Genetics, Medical College of Georgia
Olga V. Chechneva: School of Medicine, University of California
Seung-Hyuk Chung: School of Medicine, University of California
Mahendra S. Rao: NIH Center for Regenerative Medicine
David E. Pleasure: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children—Northern California
Ying Liu: University of Texas Health Science Center at Houston
Quanguang Zhang: Institute of Molecular Medicine and Genetics, Medical College of Georgia
Wenbin Deng: School of Medicine, University of California

Nature Communications, 2013, vol. 4, issue 1, 1-16

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/ncomms3196

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