Tracking stem cells using magnetic nanoparticles

Abstract

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.

Mesenchymal stem cell tracking in the intervertebral disc

“…Superparamagnetic iron oxide nanoparticles (SPIONs) consist of an iron oxide core, usually magnetite (Fe3O4) or maghemite (γFe2O3) and a biocompatible coating. Coating substrates include dextran, carboxydextran, polyethylene glycol (PEG), polystyrene and silica [77] . Iron oxide nanoparticles can be subdivided into standard SPION, 60 to 150 nm in size, and ultrasmall superparamagnetic iron oxide nanoparticles (USPION) which measure 10 to 20 nm [78,79] .…”

“…A number of contrast agents have been approved for clinical use in medical imaging. Previously, the most commonly used iron oxide nanoparticle for cell labeling was Feridex ® , which contains an iron oxide core and dextran coating [77] . Dextran coated SPIONs have been shown to be biocompatible and biodegradable via iron metabolism through Kupffer cells, located in the liver [89] .…”

“…Another widely used SPION, Resovist ® , has a carboxydextran coating [90,91] . Both these products have been discontinued from production by the pharmaceutical companies [77,92] . Other commercial products continue to be utilized, such as SiMAG ® , an SPIO with an unmodified silica surface.…”

“…T2 signal change is due to the overall effect of magnetic nanoparticles rather than total number of cells [100] . Typically, a few hundred cells are required for detection with conventional MRI sequences [77] . Stem cells are known to proliferate following transplantation, leading to dilution of the iron oxide label and loss of MR signal over time [77] .…”

“…Typically, a few hundred cells are required for detection with conventional MRI sequences [77] . Stem cells are known to proliferate following transplantation, leading to dilution of the iron oxide label and loss of MR signal over time [77] . If cells divide asymmetrically, with one daughter cell receiving the majority of nanoparticles, rapid dilution of signal can occur to an undetectable level [101] .…”