Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions

J Neurochem. 2015 Nov;135(3):539-50. doi: 10.1111/jnc.13262. Epub 2015 Sep 17.

Abstract

We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases.

Keywords: cell survival; cerebral microvascular endothelial cells; cerebral small vessel disease; oligodendrocyte; precursor cell; remyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy*
  • Cell Survival / physiology
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / therapy*
  • Endothelial Cells / transplantation*
  • Male
  • Microvessels / cytology
  • Microvessels / transplantation*
  • Oligodendroglia / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / physiology*