title: 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.
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.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, USA.
authors.forename: Naser
authors.initials: N
authors.lastname: Muja
authors.forename: Mikhal E
authors.initials: ME
authors.lastname: Cohen
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Heechul
authors.initials: H
authors.lastname: Kim
authors.forename: Assaf A
authors.initials: AA
authors.lastname: Gilad
authors.forename: Piotr
authors.initials: P
authors.lastname: Walczak
authors.forename: Tamir
authors.initials: T
authors.lastname: Ben-Hur
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001427:Bacterial Toxins; D002465:Cell Movement; D003287:Contrast Media; D003911:Dextrans; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology* / Q000628:therapy*; D005260:Female; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000473:pathology* / Q000628:therapy*; D053758:Nanoparticles; D013194:Staining and Labeling; D018709:Statistics, Nonparametric; D033581:Stem Cell Transplantation
chemical_list: D001427:Bacterial Toxins; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides