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

Nat Commun. 2013:4:2196. doi: 10.1038/ncomms3196.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / metabolism
  • Astrocytes / transplantation*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers / metabolism
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy*
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Gene Expression
  • Genes, Reporter
  • Green Fluorescent Proteins
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Injections, Intraventricular
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Stereotaxic Techniques
  • Transplantation, Heterologous

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • Nerve Tissue Proteins
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • Green Fluorescent Proteins

Associated data

  • GEO/GSE47515