Abstract
In the mid-1980s, iron oxide nanoparticles were developed as contrast agents for diagnostic imaging. In the last two decades, established methods to label cells with superparamagnetic iron oxides (SPIOs) have been developed to aid in targeted delivery and tracking of stem cell therapies. The surge in cellular therapy clinical trials for cardiovascular applications has seen a similar rise in the number of preclinical animal studies of SPIO-labeled stem cells in an effort to understand the mechanisms of cardiovascular regenerative therapy and stem cell biodistribution. The adoption of a limited number of methods of direct labeling of stem cells with SPIOs is due in large part to the desire to rapidly translate these techniques to clinical trials. In this review, we will outline the most commonly adopted methods for iron oxide labeling of stem cells for cardiovascular applications and describe strategies for magnetic resonance imaging (MRI) of magnetically labeled cells in the heart.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Weissleder R, Cheng HC, Bogdanova A, Bogdanov A, Jr. Magnetically labeled cells can be detected by MR imaging. J Magn Reson Imaging 1997;7(1):258–63.
Kraitchman DL, Heldman AW, Atalar E, et al. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 2003;107(18):2290–3.
Hill JM, Dick AJ, Raman VK, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation 2003;108(8):1009–14.
Garot J, Unterseeh T, Teiger E, et al. Magnetic resonance imaging of targeted catheter-based implantation of myogenic precursor cells into infarcted left ventricular myocardium. J Am Coll Cardiol 2003;41(10):1841–6.
Bulte JW, Kraitchman DL. Monitoring cell therapy using iron oxide MR contrast agents. Curr Pharm Biotechnol 2004;5(6):567–84.
Rickers C, Gallegos R, Seethamraju RT, et al. Applications of magnetic resonance imaging for cardiac stem cell therapy. J Interv Cardiol 2004;17(1):37–46.
Kustermann E, Roell W, Breitbach M, et al. Stem cell implantation in ischemic mouse heart: a high-resolution magnetic resonance imaging investigation. NMR Biomed 2005;18(6):362–70.
de Vries IJ, Lesterhuis WJ, Barentsz JO, et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 2005;23(11):1407–13.
Stuckey DJ, Carr CA, Martin-Rendon E, et al. Iron particles for noninvasive monitoring of bone marrow stromal cell engraftment into, and isolation of viable engrafted donor cells from, the heart. Stem Cells 2006;24(8):1968–75.
Amado LC, Schuleri KH, Saliaris AP, et al. Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy. J Am Coll Cardiol 2006;48(10):2116–24.
Ebert SN, Taylor DG, Nguyen HL, et al. Noninvasive tracking of cardiac embryonic stem cells in vivo using magnetic resonance imaging techniques. Stem Cells 2007;25(11):2936–44.
Arai T, Kofidis T, Bulte JW, et al. Dual in vivo magnetic resonance evaluation of magnetically labeled mouse embryonic stem cells and cardiac function at 1.5 t. Magn Reson Med 2006;55(1):203–9.
Frank JA, Miller BR, Arbab AS, et al. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology 2003;228:480–7.
Frank JA, Zywicke H, Jordan EK, et al. Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. Acad Radiol 2002;9:S484–S7.
Kalish H, Arbab AS, Miller BR, et al. Combination of transfection agents and magnetic resonance contrast agents for cellular imaging: relationship between relaxivities, electrostatic forces, and chemical composition. Magn Reson Med 2003;50(2):275–82.
Cahill KS, Germain S, Byrne BJ, Walter GA. Non-invasive analysis of myoblast transplants in rodent cardiac muscle. Int J Cardiovasc Imaging 2004;20(6):593–8.
Tallheden T, Nannmark U, Lorentzon M, et al. In vivo MR imaging of magnetically labeled human embryonic stem cells. Life Sci 2006;79(10):999–1006.
Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 2004;17(7):484–99.
Walczak P, Kedziorek D, Gilad AA, Lin S, Bulte JW. Instant MR labeling of stem cells using magnetoelectroporation. Magn Reson Med 2005;54(4):769–74.
Suzuki Y, Zhang S, Kundu P, Yeung AC, Robbins RC, Yang PC. In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides. Magn Reson Med 2007;57(6):1173–9.
Arbab AS, Yocum GT, Kalish H, et al. Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood 2004;104(4):1217–23.
Bulte JW, Arbab AS, Douglas T, Frank JA. Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging. Methods Enzymol 2004;386:275–99.
Walczak P, Ruiz-Cabello J, Kedziorek DA, et al. Magnetoelectroporation: improved labeling of neural stem cells and leukocytes for cellular magnetic resonance imaging using a single FDA-approved agent. Nanomedicine 2006;2(2):89–94.
Kostura L, Kraitchman DL, Mackay AM, Pittenger MF, Bulte JW. Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 2004;17(7):513–7.
Janic B, Iskander AS, Rad AM, Soltanian-Zadeh H, Arbab AS. Effects of ferumoxides-protamine sulfate labeling on immunomodulatory characteristics of macrophage-like THP-1 cells. PLoS One 2008;3(6):e2499.
Rad AM, Janic B, Iskander AS, Soltanian-Zadeh H, Arbab AS. Measurement of quantity of iron in magnetically labeled cells: comparison among different UV/VIS spectrometric methods. Biotechniques 2007;43(5):627–8, 30, 32 passim.
Pawelczyk E, Arbab AS, Pandit S, Hu E, Frank JA. Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging. NMR Biomed 2006;19(5):581–92.
Seppenwoolde JH, Viergever MA, Bakker CJ. Passive tracking exploiting local signal conservation: the white marker phenomenon. Magn Reson Med 2003;50(4):784–90.
Cunningham CH, Arai T, Yang PC, McConnell MV, Pauly JM, Conolly SM. Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magn Reson Med 2005;53(5):999–1005.
Mani V, Saebo KC, Itskovich V, Samber DD, Fayad ZA. GRadient echo Acquisition for Superparamagnetic particles with Positive contrast (GRASP): Sequence characterization in membrane and glass superparamagnetic iron oxide phantoms at 1.5 T and 3 T. Magn Reson Med 2006;55:126–35.
Stuber M, Gilson WD, Schär M, et al. Positive contrast visualization of iron oxide-labeled stem cells using inversion recovery with ON-resonant water suppression (IRON). Magn Reson Med 2007;58:1072–7.
Kraitchman DL, Bulte JW. Imaging of stem cells using MRI. Basic Res Cardiol 2008;103(2):105–13.
Mani V, Briley-Saebo KC, Hyafil F, Itskovich V, Fayad ZA. Positive magnetic resonance signal enhancement from ferritin using a GRASP (GRE acquisition for superparamagnetic particles) sequence: ex vivo and in vivo study. J Cardiovasc Magn Reson 2006;8(1):49–50.
Farrar CT, Dai G, Novikov M, et al. Impact of field strength and iron oxide nanoparticle concentration on the linearity and diagnostic accuracy of off-resonance imaging. NMR Biomed 2008;21(5):453–63.
Politi LS, Bacigaluppi M, Brambilla E, et al. Magnetic-resonance-based tracking and quantification of intravenously injected neural stem cell accumulation in the brains of mice with experimental multiple sclerosis. Stem Cells 2007;25(10):2583–92.
Nelson GN, Roh JD, Mirensky TL, et al. Initial evaluation of the use of USPIO cell labeling and noninvasive MR monitoring of human tissue-engineered vascular grafts in vivo. FASEB J 2008;22(11):3888–95.
Oude Engberink RD, van der Pol SM, Dopp EA, de Vries HE, Blezer EL. Comparison of SPIO and USPIO for in vitro labeling of human monocytes: MR detection and cell function. Radiology 2007;243(2):467–74.
Sun R, Dittrich J, Le-Huu M, et al. Physical and biological characterization of superparamagnetic iron oxide- and ultrasmall superparamagnetic iron oxide-labeled cells: a comparison. Invest Radiol 2005;40(8):504–13.
Cahill KS, Gaidosh G, Huard J, Silver X, Byrne BJ, Walter GA. Noninvasive monitoring and tracking of muscle stem cell transplants. Transplantation 2004;78(11):1626–33.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Kedziorek, D.A., Kraitchman, D.L. (2010). Superparamagnetic Iron Oxide Labeling of Stem Cells for MRI Tracking and Delivery in Cardiovascular Disease. In: Lee, R. (eds) Stem Cells for Myocardial Regeneration. Methods in Molecular Biology, vol 660. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-705-1_11
Download citation
DOI: https://doi.org/10.1007/978-1-60761-705-1_11
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-704-4
Online ISBN: 978-1-60761-705-1
eBook Packages: Springer Protocols