hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury.
Nat Commun, 2013;4:2196.
Jiang P[1], Chen C, Wang R, Chechneva OV, Chung SH, Rao MS, Pleasure DE, Liu Y, Zhang Q, Deng W
Affiliations
PMID: 23880652DOI: 10.1038/ncomms3196
Impact factor: 17.694
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.
MeSH terms
Animals; Astrocytes; Basic Helix-Loop-Helix Transcription Factors; Biomarkers; Brain Ischemia; Cell Differentiation; Cell Lineage; Cells, Cultured; Embryonic Stem Cells; Gene Expression; Genes, Reporter; Green Fluorescent Proteins; Hippocampus; Humans; Injections, Intraventricular; Male; Nerve Tissue Proteins; Oligodendrocyte Transcription Factor 2; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Stereotaxic Techniques; Transplantation, Heterologous
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