MRI tracking of intravenously transplanted human neural stem cells in rat focal ischemia model

Abstract

The present study investigated the ability of 1.5 T clinical magnetic resonance imaging (MRI) to detect ferumoxides- labeled human neural stem cells (NSCs) that had been intravenously (i.v.) injected into a rat model of focal cerebral ischemia. To detect transplanted cells, hNSCs were labeled with ferumoxide then followed by bromodeoxyuridine (BrdU) prior to transplantation. In the rat ischemia–human NSC group, human NSCs (4 × 10 6 cells in 5 ml PBS) were injected via tail vein 24 h after middle cerebral artery occlusion (MCAo), and the brains of the rats were scanned using a 1.5 T MRI unit over a period of 4 weeks (1 day before MCAo, then 1 and 3 days after cell injection, and weekly thereafter). In histologic sections, transplanted cells were identified by Prussian blue and anti-BrdU fluorescence staining. Regions with hypointense signals on T2-weighted and 3D gradient echo MR images corresponded with areas stained by Prussian blue, which suggested the presence of superparamagnetic iron oxide (SPIO) nanoparticles within the engrafted cells. Hypointense areas on MR images were observed in peri-infarct areas 3 days after cell injection. The findings indicate that 1.5 T MRI has sufficient sensitivity to track engrafted stem cells in vivo.