Neural precursors exhibit distinctly different patterns of cell migration upon transplantation during either the acute or chronic phase of EAE: A serial MR imaging study

Naser Muja, Mikhal E. Cohen, Jiangyang Zhang, Heechul Kim, Assaf A. Gilad, Piotr Walczak, Tamir Ben-Hur, Jeff W.M. Bulte

Research output: Contribution to journalArticle

Abstract

As the complex pathogenesis of multiple sclerosis contributes to spatiotemporal variations in the trophic micromilieu of the central nervous system, the optimal intervention period for cell-replacement therapy must be systematically defined. We applied serial, 3D high-resolution magnetic resonance imaging to transplanted neural precursor cells (NPCs) labeled with superparamagnetic iron oxide nanoparticles and 5-bromo-2-deoxyuridine, and compared the migration pattern of NPCs in acute inflamed (n = 10) versus chronic demyelinated (n = 9) brains of mice induced with experimental allergic encephalomyelitis (EAE). Serial in vivo and ex-vivo 3D magnetic resonance imaging revealed that NPCs migrated 2.5 ± 1.3 mm along the corpus callosum in acute EAE. In chronic EAE, cell migration was slightly reduced (2.3 ± 1.3 mm) and only occurred in the lateral side of transplantation. Surprisingly, in 6/10 acute EAE brains, NPCs were found to migrate in a radial pattern along RECA-1+ cortical blood vessels, in a pattern hitherto only reported for migrating glioblastoma cells. This striking radial biodistribution pattern was not detected in either chronic EAE or disease-free control brains. In both acute and chronic EAE brain, Iba1+ microglia/macrophage number was significantly higher in central nervous system regions containing migrating NPCs. The existence of differential NPC migration patterns is an important consideration for implementing future translational studies in multiple sclerosis patients with variable disease. Magn Reson Med, 2011.

Original languageEnglish (US)
Pages (from-to)1738-1749
Number of pages12
JournalMagnetic resonance in medicine
Volume65
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • SPIO
  • blood vessel
  • cell tracking
  • multiple sclerosis
  • neural stem cell

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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