Abstract
Cell tracking by magnetic resonance imaging (MRI) is an essential tool to understand the integration and migration of transplanted cells in vivo. At present, however, techniques to visualize cell transplants in patients are fairly limited and further development of cellular MRI is needed to advance the monitoring of grafted cells. The use of contrast agents to pre-label cells prior to transplantation is currently needed as transplanted cells integrate seamlessly into existing parenchyma and hence are indistinguishable from host cells. The development of appropriate contrast agents, as well as their in vitro incorporation into cells, is key to visualizing transplanted cells in vivo. We describe here procedures regarding how the in vitro incorporation of MR contrast agents can be tested, how they might affect cellular functions and how we can determine if sufficient contrast agent has been incorporated to allow detection. Before this technique can find its clinical application, in vitro and preclinical in vivo studies need to be conducted to determine the safety and specificity of this approach.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Modo. M. (2008). Brain repair how stem cells are changing neurology. Bull. Soc. Sci. Med. Grand Duche Luxemb. 2, 217–257.
Modo, M. (2008). Noninvasive imaging of transplanted cells. Curr. Opin. Organ Transplant 13, 654–658.
Modo, M., Hoehn, M., Bulte, J.W. (2005) Cellular MR imaging. Mol. Imaging 4, 143–164.
Bulte, J.W., Kraitchman, D.L. (2004) Monitoring cell therapy using iron oxide MR contrast agents. Curr. Pharm. Biotechnol. 5, 567–584.
Shapiro, E.M., Sharer, K., Skrtic, S., Koretsky, A.P. (2006) In vivo detection of single cells by MRI. Magn. Reson. Med. 55, 242–249.
Modo, M., Cash, D., Mellodew, K., Williams, S.C., Fraser, S.E., Meade, T.J., Price, J., Hodges, H. (2002) Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging. Neuroimage 17, 803–811.
Mulder, W.J., Koole, R., Brandwijk, R.J., Storm, G., Chin, P.T., Strijkers, G.J., de Mello Donega, C., Nicolay, K., Griffioen, A.W. (2006) Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Lett. 6, 1–6.
Daldrup-Link, H.E., Rudelius, M., Metz, S., Piontek, G., Pichler, B., Settles, M., Heinzmann, U., Schlegel, J., Oostendorp, R.A., Rummeny, E.J. (2004) Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy. Eur. J. Nucl. Med. Mol. Imaging 31, 1312–1321.
Terreno, E., Geninatti Crich, S., Belfiore, S., Biancone, L., Cabella, C., Esposito, G., Manazza, A.D., Aime, S. (2006) Effect of the intracellular localization of a Gd-based imaging probe on the relaxation enhancement of water protons. Magn. Reson. Med. 55, 491–497.
de Vries, I.J., Lesterhuis, W.J., Barentsz, J.O., Verdijk, P., van Krieken, J.H., Boerman, O.C., Oyen, W.J., Bonenkamp, J.J., Boezeman, J.B., Adema, G.J., Bulte, J.W., Scheenen, T.W., Punt, C.J., Heerschap, A., Figdor, C.G. (2005) Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat. Biotechnol. 23, 1407–1413.
Zhu, J., Zhou, L., XingWu, F. (2006) Tracking neural stem cells in patients with brain trauma. N. Engl. J. Med. 355, 2376–2378.
Karabulut, N., Elmas, N. (2006) Contrast agents used in MR imaging of the liver. Diagn. Interv. Radiol. 12, 22–30.
Ahrens, E.T., Flores, R., Xu, H., Morel, P.A. (2005) In vivo imaging platform for tracking immunotherapeutic cells. Nat. Biotechnol. 23, 983–987.
Perls, M. (1867) Nachweis von Eisenoxyd in gewissen Pigmenten. Virchows Archiven der Pathologie, Anatomie und Physiologie 39, 42–48.
Brekke, C., Morgan, S.C., Lowe, A.S., Meade, T.J., Price, J., Williams, S.C., Modo, M. (2007) The in vitro effects of a bimodal contrast agent on cellular functions and relaxometry. NMR Biomed. 20(2), 77–89.
Modo, M., Beech, J.S., Meade, T.J., Williams, S.C., Price, J. (2009) A chronic 1 year assessment of MRI contrast agent-labelled neural stem cell transplants in stroke. Neuroimage 47(Suppl. 2), T133–142.
Friend, J.R., Wu, F.J., Hansen, L.K., Remmel, R.P., Hu, W.S. (1999) Formation and characterization of hepatocyte spheroids. In: Morgan, J.R., Yarmush. M.L. (eds.), Methods in Molecular Medicine: Tissue Engineering Methods and Protocols (pp. 248–249). Totowa, N.J: Humana Press Inc.
Mitry, R.R., Hughes, R.D., Bansal, S., Lehec, S.C., Wendon, J.A., Dhawan, A. (2005) Effects of serum from patients with acute liver failure due to paracetamol overdose on human hepatocytes in vitro. Transplant. Proc. 37, 2391–2394.
Puppi, J., Mitry, R.R., Modo, M., Dhawan, A., Raja, K., Hughes, R.D. (in press) Use of clinically-approved iron oxide MRI contrast agent to label human hepatocytes. Cell Transplant.
Kostura, L., Kraitchman, D.L., Mackay, A.M., Pittenger, M.F., Bulte, J.W. (2004) Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed. 17, 513–517.
Acknowledgements
MM is currently supported by a RCUK fellowship. Funding for the MR imaging of cell transplants by NIBIB Quantum Grant (1 P20 EB007076-01), EU FP VII (201842 – ENCITE) and MRC (G0802552) is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Modo, M. (2011). Tracking Transplanted Cells by MRI – Methods and Protocols. In: Schröder, L., Faber, C. (eds) In vivo NMR Imaging. Methods in Molecular Biology, vol 771. Humana Press. https://doi.org/10.1007/978-1-61779-219-9_35
Download citation
DOI: https://doi.org/10.1007/978-1-61779-219-9_35
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-218-2
Online ISBN: 978-1-61779-219-9
eBook Packages: Springer Protocols