Tracking of iron-labeled human neural stem cells by magnetic resonance imaging in cell replacement therapy for Parkinson's disease

Abstract

Human neural stem cells (hNSCs) derived from the ventral mesencephalon are powerful research tools and candidates for cell therapies in Parkinson's disease. However, their clinical translation has not been fully realized due, in part, to the limited ability to track stem cell regional localization and survival over long periods of time after in vivo transplantation. Magnetic resonance imaging provides an excellent non-invasive method to study the fate of transplanted cells in vivo. For magnetic resonance imaging cell tracking, cells need to be labeled with a contrast agent, such as magnetic nanoparticles, at a concentration high enough to be easily detected by magnetic resonance imaging. Grafting of human neural stem cells labeled with magnetic nanoparticles allows cell tracking by magnetic resonance imaging without impairment of cell survival, proliferation, self-renewal, and multipotency. However, the results reviewed here suggest that in long term grafting, activated microglia and macrophages could contribute to magnetic resonance imaging signal by engulfing dead labeled cells or iron nanoparticles dispersed freely in the brain parenchyma over time.

Keywords: Parkinson's disease; human neural stem cells; magnetic nanoparticles; magnetic resonance imaging; stem cell transplantation.

Figure 1

hVM-MNPs labeled cells. Fluorescence micrographs showing human ventral midbrain (hVM) cells labeled with magnetic nanoparticles (MNPs) marked in green. Nuclei are shown in blue stained with Hoechst. Scale bar: 20 μm.

Figure 2

MRI of hVM-MNP labeled cells transplanted into rat brain. Two consecutive in vivo magnetic resonance images of hVM cell suspensions (3 × 105 cells) transplanted into the left (hVM cells, L) and right (hVM-MNP labeled cells, R) striata. MRI was performed eight weeks after cell transplantation. hVM-MNP labeled cells can be easily detected in coronal T2*-weighted images as dark hypointense signals in the area where the cells have been injected (arrows). No MRI signal was detected when unlabeled hVM cells were transplanted (left striatum, L). Scale bar: 2 mm. hVM: Human ventral midbrain; MNP: magnetic nanoparticle; MRI: magnetic resonance imaging; R: right stratum.