The role of CXCR4 signaling in the migration of transplanted oligodendrocyte progenitors into the cerebral white matter

Ghazal Banisadr*, Terra J. Frederick, Caroline Freitag, Dongjun Ren, Hosung Jung, Stephen D. Miller, Richard J. Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Enhancing the ability of either endogenous or transplanted oligodendrocyte progenitors (OPs) to engage in myelination may constitute a novel therapeutic approach to demyelinating diseases of the brain. It is known that in adults neural progenitors situated in the subventricular zone of the lateral ventricle (SVZ) are capable of generating OPs which can migrate into white matter tracts such as the corpus callosum (CC). We observed that progenitor cells in the SVZ of adult mice expressed CXCR4 chemokine receptors and that the chemokine SDF-1/CXCL12 was expressed in the CC. We therefore investigated the role of chemokine signaling in regulating the migration of OPs into the CC following their transplantation into the lateral ventricle. We established OP cell cultures from Olig2-EGFP mouse brains. These cells expressed a variety of chemokine receptors, including CXCR4 receptors. Olig2-EGFP OPs differentiated into CNPase-expressing oligodendrocytes in culture. To study the migratory capacity of Olig2-EGFP OPs in vivo, we transplanted them into the lateral ventricles of mice. Donor cells migrated into the CC and differentiated into mature oligodendrocytes. This migration was enhanced in animals with Experimental Autoimmune Encephalomyelitis (EAE). Inhibition of CXCR4 receptor expression in OPs using shRNA inhibited the migration of transplanted OPs into the white matter suggesting that their directed migration is regulated by CXCR4 signaling. These findings indicate that CXCR4 mediated signaling is important in guiding the migration of transplanted OPs in the context of inflammatory demyelinating brain disease.

Original languageEnglish (US)
Pages (from-to)19-27
Number of pages9
JournalNeurobiology of Disease
Volume44
Issue number1
DOIs
StatePublished - Oct 2011

Keywords

  • Chemoattraction
  • Chemokine
  • Chemokine receptor
  • Multiple sclerosis
  • Oligodendrocyte
  • Progenitor cell
  • White matter

ASJC Scopus subject areas

  • Neurology

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