No abstract

Noninvasive monitoring of stem cells, using high-resolution molecular imaging, will be instrumental to improve clinical neural transplantation strategies. We show that labeling of human central nervous system stem cells grown as neurospheres with magnetic nanoparticles does not adversely affect survival, migration, and differentiation or alter neuronal electrophysiological characteristics. Using MRI, we show that human central nervous system stem cells transplanted either to the neonatal, the adult, or the injured rodent brain respond to cues characteristic for the ambient microenvironment resulting in distinct migration patterns. Nanoparticlelabeled human central nervous system stem cells survive long-term and differentiate in a site-specific manner identical to that seen for transplants of unlabeled cells. We also demonstrate the impact of graft location on cell migration and describe magnetic resonance characteristics of graft cell death and subsequent clearance. Knowledge of migration patterns and implementation of noninvasive stem cell tracking might help to improve the design of future clinical neural stem cell transplantation.superparamagnetic iron oxide ͉ stem cell biology A dvances in neural transplantation have paved the way for clinical trials aimed at restoring brain function in diseases, such as Parkinson's (1-3) and Huntington's (4), and stroke (5). The success of these trials for neurological diseases will depend not only on patient selection criteria and on choosing the right cell type, but also on the timing and site of transplantation. Both variables can influence the transplanted stem cells' migration pattern and subsequent differentiation (6, 7). Therefore, long-term monitoring of the graft in relation to the evolving lesion will be crucial. MRI, with its high spatial resolution, is the ideal modality for in vivo cell tracking. Tagging cells with superparamagnetic iron oxide (SPIO) nanocomposites has been shown to induce sufficient MR cell contrast for in vivo imaging of neural cell migration (8,9). Previous studies have demonstrated its application to track stem cells after stroke, but these were done with non-human stem cells and lacked in-depth analysis of the SPIO effect on stem cell biology (10, 11).Before this method can be considered to label human neural stem cells for clinical application, further analysis of the effects of SPIO on the biology of human stem cells are needed. For example, it has been described that Feridex, a SPIO reagent approved by the United States Food and Drug Administration for human use, inhibits mesenchymal stem cells from differentiating into chondrocytes (12), emphasizing the need for in-depth analysis of the influence of magnetic labeling on stem cell biology.We investigated the effects of SPIO labeling on human central nervous system stem cells grown as neurospheres (hCNS-SCns) (6, 13-15) in vitro and in vivo. We show that SPIO-labeled hCNS-SCns proliferate and differentiate normally in vitro and exhibit neuronal electrophysiological characteristics. We th...

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