Conserved fate and function of ferumoxides-labeled neural precursor cells in vitro and in vivo

Recent progress in cell therapy research for brain diseases has raised the need for non-invasive monitoring of transplanted cells. For therapeutic application in multiple sclerosis, transplanted cells need to be tracked both spatially and temporally, in order to assess their migration and survival in the host tissue. Magnetic resonance imaging (MRI) of superparamagnetic iron oxide-(SPIO)-labeled cells has been widely used for high resolution monitoring of the biodistribution of cells after transplantation into the central nervous system (CNS). Here we labeled mouse glial-committed neural precursor cells (NPCs) with the clinically approved SPIO contrast agent ferumoxides and examined their survival and differentiation in vitro, as well as their functional response to environmental signals present within the inflamed brain of experimental autoimmune encephalomyelitis (EAE) mice in vivo. We show that ferumoxides labeling does not affect NPC survival and pluripotency in vitro. Following intracerebroventricular (ICV) transplantation in EAE mice, ferumoxides-labeled NPCs responded to inflammatory cues in a similar fashion as unlabeled cells. Ferumoxides-labeled NPCs migrated over comparable distances in white matter tracts and differentiated equally into the glial lineages. Furthermore, ferumoxides-labeled NPCs inhibited lymph node cell proliferation in vitro, similarly to non-labeled cells, suggesting a preserved immunomodulatory function. These results demonstrate that ferumoxides-based MRI cell tracking is well suited for non-invasive monitoring of NPC transplantation.