Preparation of Magnetically Labeled Cells for Cell Tracking by Magnetic Resonance Imaging
Introduction
Magnetic resonance (MR) tracking of magnetically labeled cells following transplantation or transfusion is a rapidly evolving new field. At the one hand, MR cell tracking, with its excellent spatial resolution, can be used as a noninvasive tool to provide unique information on the dynamics of cell movement within and from tissues in animal disease models. Alternatively, MR cell tracking may be applied in the future to monitor (stem) cell therapy in patients. Both approaches require magnetic labeling of the cells of choice for the particular study. It is the aim of this review to provide methods and protocols for the preparation of magnetically labeled cells as well as methods for analysis and evaluation of cell labeling. Due to its biocompatibility and strong effects on T2(∗) relaxation, iron oxide nanoparticles are now the MR contrast agent of choice for cell labeling, and several methods are provided that shuttle sufficient amounts into cells. Now that magnetic labeling methods have been developed and optimized it is expected that MRI cell tracking will find broad applications in monitoring transplantation protocols for cell-based therapy.
Section snippets
Cell Transplantation
The administration or transplantation of exogenous or autologous therapeutic cells has been pursued as a very active research area over the last decade, and, for progenitor and stem cell therapy, remarkable progress has been obtained in animal disease models. Because of its limited regenerative capacity, the central nervous sytem (CNS) so far has received the most interest for cell (replacement) therapy. For instance, transplantation of mouse embryonic stem (ES), which was directed in vitro
Superparamagnetic Iron Oxides
As for MR contrast agents, gadolinium is the most effective paramagnetic contrast agent, owing to its seven unpaired electrons, but its relaxivity (effectiveness in increasing the MR relaxation rate per mM of metal) is far lower than the so-called superparamagnetic iron oxides (SPIOs). Unlike gadolinium, which is potentially toxic in unchelated form and is designed not to stay within the body for prolonged times, iron oxides are composed of biocompatible iron.20 For magnetic labeling of cells,
Preparation of Magnetically Labeled Cells
For efficient uptake of magnetic nanoparticles in nonphagocytic cells, the contrast agent needs to be optimized or modified to have an appropriate outer surface layer that not only binds to cellular membranes, but also induces internalization of the particles into the cytoplasm. Particles that do not internalize and stay attached to the outer cell membrane are likely to interfere with cell surface interactions (including cell homing into tissues), may detach easily from the membrane, or can be
Magnetically Labeled Cells: Methods of Analysis
From the previous sections, it is clear that several alternative methods have now been developed for a successful preparation of magnetically labeled cells. Time will tell us which method will be preferred by most investigators, and which method will be eventually implemented in a clinical setting. Regardless of the method employed, the analysis and evaluation of magnetic labeling will follow similar protocols. As mentioned earlier, an important qualitative method of analysis is Prussian Blue
Magnetically Labeled Cells: Detection Limits
A number of studies have indicated that MRI cell tracking of small numbers of labeled cells or even single labeled cells may be feasible. At higher magnetic fields, single T cells were detected with a good correlation of the corresponding fluorescent images.87 Single magnetodendrimer-labeled oocytes, which are large mammalian cells, were imaged at 11.7 T, and clear distinction between the nuclear and cellular compartments was achieved.88 At a clinical field strength of 1.5 T, using customized
Acknowledgements
J.W.M.B. is supported by grants RO1 NS045062 (NIH) and PP0922 (Multiple Sclerosis Society).
References (89)
- et al.
Brain Res.
(2003) - et al.
Exp. Neurol.
(2001) - et al.
Exp. Neurol.
(1998) - et al.
Exp. Neurol.
(1993) - et al.
Magn. Reson. Imaging
(1999) - et al.
J. Immunol. Methods
(2001) - et al.
Acad. Radiol.
(2002) - et al.
Neuroscience
(2003) - et al.
Ann. Neurol.
(2003) - et al.
Blood
(2003)
Biomaterials
Biomed. Pharmacother.
Biophys. J.
Nat. Med.
Proc. Natl. Acad. Sci. USA
Nature
Proc. Natl. Acad. Sci. USA
Movement Disord.
J. Neurosci.
Nat. Biotechnol.
Proc. Natl. Acad. Sci. USA
Nat. Med.
Science
Proc. Natl. Acad. Sci. USA
J. Comp. Neurol.
Neurology
Science
Proc. Natl. Acad. Sci. USA
Am. J. Roentgenol.
Radiology
Radiology
N. Engl. J. Med.
Radiology
Radiology
Radiology
Magn. Reson. Med.
J. Magn. Reson. Imaging
J. Magn. Reson. Imaging
Neuroreport
Bioconjug. Chem.
Nat. Biotechnol.
Bioconjug. Chem.
Biotechniques
Proc. Intl. Soc. Mag. Reson. Med.
Cited by (176)
Magnetic particle imaging
2021, Magnetic Materials and Technologies for Medical ApplicationsNanoengineering of stem cells for musculoskeletal regeneration
2020, Nanoengineering in Musculoskeletal RegenerationMagnetic Modification of Cells
2016, Engineering of Nanobiomaterials: Applications of Nanobiomaterials<sup>19</sup>F MRI-fluorescence imaging dual-modal cell tracking with partially fluorinated nanoemulsions
2022, Frontiers in Bioengineering and Biotechnology