Editors' ChoiceNanomedicine

Forging New Approaches to Stem Cell Tracking

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Science Translational Medicine  18 Sep 2013:
Vol. 5, Issue 203, pp. 203ec153
DOI: 10.1126/scitranslmed.3007554

Tracking stem cells in the brain will be an important component of cell therapy clinical trials. Traditional approaches to cell labeling, such as fluorophores, are not ideal for use in the human brain because the light cannot penetrate the thickness of the tissues. In response, Gutova and colleagues describe ultrasmall super paramagnetic iron oxide nano particles (USPIOs) for tagging and tracking neural stem cells (NSCs) by means of magnetic resonance imaging (MRI). Translation of this approach would allow clinicians to see how stem cells home to glioma tumors through serial MRI scans.

To make USPIOs such as ferumoxytol more biocompatible with NSCs, the researchers optimized the ratios for the formation of heparin, protamine sulfate, and ferumoxytol (HPF) particles. MRI studies in orthotopic glioma tumor mouse models revealed that both intracerebrally and intravenously delivered NSCs loaded with HPFs could be seen homing near and within brain tumors. On the basis of these studies, Gutova et al. were able to determine the amount of iron needed to successfully and safely image NSCs clinically. At doses higher than expected for use in humans, no iron-associated toxicity was seen at 4 and 12 weeks after SPIO administration, and any immune cell infiltration eventually resolved over the 12-week study period.

Ferumoxytol is currently approved for the treatment of iron-deficiency anemia and is also being evaluated for MRI in many cancer clinical trials. Both NSC tumor-targeting therapy and the use of SPIO nanoparticles to track them will require continued optimization and evaluation. However, the work described in this study laid the preclinical groundwork that has already contributed to the translation of ferumoxytol-based nanoparticles into clinical use as agents for labeling human NSCs.

M. Gutova et al., Magnetic resonance imaging tracking of ferumoxytol-labeled human neural stem cells: Studies leading to clinical use. Stem Cells Transl. Med., published online 6 September 2013 (10.5966/sctm.2013-0049) [Abstract]

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