Bone-marrow cell therapy induces differentiation of radial glia-like cells and rescues the number of oligodendrocyte progenitors in the subventricular zone after global cerebral ischemia

Stem Cell Res. 2013 Mar;10(2):241-56. doi: 10.1016/j.scr.2012.11.009. Epub 2012 Dec 9.

Abstract

The subventricular zone (SVZ) is recognized as one of the neurogenic regions in the adult mammalian central nervous system and the presence of cells that share similar characteristics with developmental radial glia, the radial glia-like cells (RGLCs) has been demonstrated in this region. In this study, we investigated whether and how SVZ cells respond to global ischemia and/or to the intravenous transplant of bone-marrow mononuclear cells (BMMCs). Adult rats were subjected to bilateral common carotid ligation (BCCL) and after 1 day 2×10(7) BMMCs or saline injection. The BMMC transplant stimulated a transitory increase in the proliferation of SVZ cells in the BCCL group. We observed a significant increase in the number of RGLCs 3days after ischemia, in both BCCL and BCCL+BMMC groups. However, this increase persisted in the subsequent days only in BCCL animals that received the transplant. BMMC transplantation also inhibits the reduction of NG2-positive oligodendrocyte progenitors in the SVZ observed in the BCCL group. Interestingly, brain-derived neurotrophic factor (BDNF) expression was up-regulated in the SVZ in the treated animals, but not in the other groups. These data thus suggest that BMMC transplantation modulates the phenotype of RGLCs/progenitors in the SVZ and could have a protective role after ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Transplantation*
  • Brain / pathology
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy*
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Carotid Artery, Common / pathology
  • Cell Count
  • Cell Differentiation*
  • Cell Proliferation
  • Cerebral Ventricles / blood supply
  • Cerebral Ventricles / pathology*
  • Gene Expression Regulation
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / transplantation
  • Ligation
  • Male
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • RNA, Messenger