Abstract
Methods to monitor transplanted stem cells in vivo are of great importance for potential therapeutic applications. Of particular interest are methods allowing noninvasive detection of stem cells throughout the body. Magnetic resonance imaging (MRI) is a tool that would allow detection of cells in nearly any tissue in the body and is already commonly used in the clinic. MRI tracking of stem cells is therefore feasible and likely to be easily adapted to patients receiving donor cells. Patients with Duchenne muscular dystrophy are good candidates for stem cell therapy, given the naturally regenerative nature of skeletal muscle, which repairs damage by employing endogenous stem cells from the muscle interstitium to regenerate muscle fibers throughout adulthood. We describe methods for labeling stem cells with superparamagnetic iron oxide nanoparticles (SPIO) to enhance MRI contrast, injecting them locally into skeletal and cardiac muscle, or systemically in mouse models for Duchenne muscular dystrophy, and tracking them in muscle tissue of live mice following injection. We focus on the use of whole body MRI to detect stem cells, as this is necessary for conditions such as muscular dystrophy, in which affected tissues are present throughout the body and systemic delivery of stem cells may be necessary. Emphasis is placed on the development of an MRI coil that is field of view (FOV) adjustable and can be used for both whole body imaging to determine stem cell localization as well as subsequent focusing on smaller, local regions where stem cells are present to obtain high-resolution images. We discuss the coil design and its significance for stem cell tracking. We also describe methods for labeling stem cells with a fluorescent dye and for tracking them in postmortem tissue specimens with fluorescent microscopy to correlate, compare, and contrast with results of whole body MRI in preclinical studies.
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References
Rogers W, Meyer C, Kramer C (2006) Technology insight: in vivo cell tracking by use of MRI. Nat Clin Pract Cardiovasc Med 3:554–562
Waters E, Wickline S (2008) Contrast agents for MRI. Basic Res Cardiol 103:114–121
Bowen C, Zhang X, Saab G et al (2002) Application of the static dephasing regime theory to uperparamagnetic iron-oxide loaded cells. Magn Reson Med 48:52–61
Odintsov B, Chun J, Mulligan J et al (2011) 14.1 T whole body MRI for detection of mesoangioblast stem cells in a murine model of Duchenne muscular dystrophy. Magn Reson Med 66:1704–1714
Odintsov B (2011) Tunable radiofrequency coil. US Patent US 2010/10013483 A1, 1 Nov 2011
Doty F, Entzminger G, Kulkarni J et al (2007) Radio frequency coil technology for small-animal MRI. NMR Biomed 20:304–345
Jing X, Yang L, Duan X et al (2008) In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection. Joint Bone Spine 75:432–438
Hoehn M, Kustermann E, Blunk J et al (2002) Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci U S A 99:16267–16272
Syková E, Jendelová P, Herynek V (2009) MR tracking of stem cells in living recipients. Methods Mol Biol 549:197–215
Berry S, Liu J, Chaney E et al (2007) Multipotential ADM stem cell therapy in the mdx/utrn−/− mouse model for Duchenne muscular dystrophy. Regen Med 2:275–288
Grady R, Teng H, Nichol M et al (1997) Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy. Cell 90:729–738
Deconinck A, Rafael J, Skinner J (1997) Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell 90:717–727
Gruetter R, Tkáč I (2000) Field mapping without reference scan using asymmetric echo-planar techniques. Magn Reson Med 43:319–323
Brozoski T, Odintsov B, Bauer C (2012) Gamma-aminobutyric acid and glutamic acid levels in the auditory pathway of rats with chronic tinnitus: a direct determination using high resolution point-resolved proton magnetic resonance spectroscopy (1H-MRS). Front Syst Neurosci 6:9
Byung H, Cho S, Park J et al (2010) Synthetic dimyristoylphosphatidylcholine liposomes assimilating into high-density lipoprotein promote regression of atherosclerotic lesions in cholesterol-fed rabbits. Exp Biol Med 235:1194–1203
Wang L, Kamath A, Frye J et al (2012) Aorta-derived ADMs differentiate into oligodendrocytes by inhibition of the Rho kinase signaling pathway. Stem Cells Dev 21(7):1069–1089
Frank J, Miller B, Arbab A et al (2003) Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology 228:480–487
Frank J, Zywicke H, Jordan E et al (2002) Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. Acad Radiol Suppl 2:S484–S487
Driehuys B, Hedlund L (2007) Imaging techniques for small animal models of pulmonary disease: MR microscopy. Toxicol Pathol 35:49–58
Driehuys B, Nouls J, Badea A et al (2008) Small animal imaging with magnetic resonance microscopy. ILAR J 49:35–53
Loebinger M, Kyrtatos P, Turmaine M et al (2009) Magnetic resonance imaging of mesenchymal stem cells homing to pulmonary metastases using biocompatible magnetic nanoparticles. Cancer Res 69:8862–8867
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Odintsov, B., Chun, J.L., Berry, S.E. (2013). Whole Body MRI and Fluorescent Microscopy for Detection of Stem Cells Labeled with Superparamagnetic Iron Oxide (SPIO) Nanoparticles and DiI Following Intramuscular and Systemic Delivery. In: Turksen, K. (eds) Imaging and Tracking Stem Cells. Methods in Molecular Biology, vol 1052. Humana Press, Totowa, NJ. https://doi.org/10.1007/7651_2013_13
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DOI: https://doi.org/10.1007/7651_2013_13
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