Magnetic resonance imaging detects differences in migration between primary and immortalized neural stem cells

RATIONALE AND OBJECTIVES: The study was performed to evaluate the effect of magnetic resonance imaging (MRI) contrast agent (super paramagnetic iron oxide SPIO]) on differentiation and migration of primary murine neural stem cells (NSCs) in comparison to a neural stem cell line (C17.2). Because detection of labeled cells depends on the concentration of SPIO particles per imaging voxel, the study was performed at various concentrations of SPIO particles to determine the concentration that could be used for in vivo detection of small clusters of grafted cells. MATERIALS AND METHODS: Murine primary NSCs or C17.2 cells were labeled with different concentrations of SPIO particles (0, 25, 100, and 250 mug Fe/mL) and in vitro assays were performed to assess cell differentiation. In vivo MRI was performed 7 weeks after neonatal transplantation of labeled cells to evaluate the difference in migration capability of the two cell populations. RESULTS: Both the primary NSCs and the C17.2 cells differentiated to similar number of neurons (Map2ab-positive cells). Similar patterns of engraftment of C17.2 cells were seen in transplanted mice regardless of the SPIO concentration used. In vivo MRI detection of grafted primary and C17.2 cells was only possible when cells were incubated with 100 mug/mL or higher concentration of SPIO. Extensive migration of C17.2 cells throughout the brain was observed, whereas the migration of the primary NSCs was more restricted. CONCLUSIONS: Engraftment of primary NSCs can be detected noninvasively by in vivo MRI, and the presence of SPIO particles do not affect the viability, differentiation, or engraftment pattern of the donor cells.