Stem cell therapies offer great promise for many diseases, especially those without current effective treatments. It is believed that noninvasive imaging techniques, which offer the ability to track the status of cells after transplantation, will expedite progress in this field and help to achieve maximized therapeutic effect. Today’s biomedical imaging technology allows for real-time, noninvasive monitoring of grafted stem cells including their biodistribution, migration, survival, and differentiation, with magnetic resonance imaging (MRI) of nanoparticle-labeled cells being one of the most commonly used techniques. Among the advantages of MR cell tracking are its high spatial resolution, no exposure to ionizing radiation, and clinical applicability. In order to track cells by MRI, the cells need to be labeled with magnetic nanoparticles, for which many types exist. There are several cellular labeling techniques available, including simple incubation, use of transfection agents, magnetoelectroporation, and magnetosonoporation. In this overview article, we will review the use of different magnetic nanoparticles and discuss how these particles can be used to track the distribution of transplanted cells in different organ systems. Caveats and limitations inherent to the tracking of nanoparticle-labeled stem cells are also discussed.

An array of 33 prototype polypeptides was examined as putative contrast agents that can be distinguished from each other based on the chemical exchange saturation transfer (CEST) mechanism. These peptides were chosen based on predictions of the chemical exchange rates of exchangeable amide, amine, and hydroxyl protons that produce this contrast, and tested at 11.7T for their CEST suitability. Artificial colors were assigned to particular amino acid units (lysine, arginine, threonine, and serine) based on the separate resonance frequencies of these exchangeable protons. The magnitude of the CEST effect could be fine-tuned by altering the amino acid sequence, and these three exchangeable groups could be distinguished in an MR phantom based on their different chemical shifts ("colors").

MRI is used for tracking of superparamagnetic iron oxide (SPIO)-labeled neural stem cells (NSCs). Studies have shown that long-term MR tracking of rapidly dividing cells underestimates their migration distance. Time-lapse microscopy of random cellular motility and cell division was performed to evaluate the effects of SPIO-labeling on NSC migration. Labeled cells divided symmetrically, and exhibited no changes in cell viability, proliferation, or apoptosis. However, SPIO-labeling resulted in decreased motility of NSCs as compared to unlabeled controls. When SPIO-labeled NSCs and human induced pluripotent stem cells (iPSCs) were transplanted into mouse brain, rapid exocytosis of SPIO by live cells was observed as early as 48 hours post-engraftment, with SPIO-depleted cells showing the farthest migration distance. As label dilution is negligible at this early time point, we conclude that MRI underestimation of cell migration can also occur as a result of reduced cell motility, which appears to be mitigated following SPIO exocytosis.