Abstract
Recent developments in stem cell and gene therapy will require methods to monitor stem cell survival and integration repeatedly and non-invasively with a high temporal and spatial resolution in vivo. The aim of this study was to visualise embryonic and neuronal stem cells with standard contrast agents using a conventional clinical 1.5-Tesla scanner. We therefore modified standard transfection protocols including lipofection (Lipofectin and Lipofectamine) and calcium phosphate transfection for the efficient uptake of paramagnetic particles [gadolinium-diethylene triamine penta-acetic acid (Gd-DTPA)] in stem cells. Using this approach we obtained intracellular labelling efficiencies of up to 83%. Neither the proliferation capacity nor the differentiation efficiency was affected. Identical differentiation of labelled and unlabelled embryonic and neuronal cells was observed. The established labelling techniques used in this study displayed high labelling efficiencies in embryonic and neuronal stem cells without any alterations of cellular biology; therefore this approach might be a suitable method for targeting stem cells.
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Schwarz EJ, Alexander GM, Prockop DJ, Azizi SA. Multipotential marrow stromal cells transduced to producel-DOPA: engraftment in a rat model of Parkinson disease. Hum Gene Ther 1999; 10:2539–2549.
Nishino H, Borlongan CV. Restoration of function by neural transplantation in the ischemic brain. Prog Brain Res 2000; 127:461–476.
Kondziolka D, Wechsler L, Goldstein L, Meltzer C, Thulborn KR, Gebel J, Jannetta P, DeCesare S, Elder EM, McGrogan M, Reitman MA, Bynum L. Transplantation of cultured human neuronal cells for patients with stroke. Neurology 2000; 55:565–569.
Johnson GA, Benveniste H, Black RD, Hedlund LD, Maronpot RR, Smith BR. Histology by magnetic resonance microscopy. Magn Reson Q 1993; 9:1–30.
Smith B, Johnson G, Groman E, Linney E. Magnetic resonance microscopy of mouse embryos. Proc Natl Acad Sci U S A 1994; 91:3530–3533.
Jacobs R, Fraser S. Magnetic resonance microscopy of embryonic cell lineages and movements. Science 1994; 263:681–684.
Weissleder R, Cheng HC, Bogdanova A, Bogdanov A Jr. Magnetically labeled cells can be detected by MR imaging. J Magn Reson Imaging 1997; 7:258–263.
Högemann D, Josephson L, Weissleder R, Basilion JP. Improvement of MRI probes to allow efficient detection of gene expression. Bioconjug Chem 2000; 11:941–946.
Yeh TC, Zhang W, Ildstad ST, Ho C. In vivo dynamic MRI tracking of rat T-cells labeled with superparamagnetic iron-oxide particles. Magn Reson Med 1995; 33:200–208.
Schoepf U, Marecos EM, Melder RJ, Jain RK, Weissleder R. Intracellular magnetic labeling of lymphocytes for in vivo trafficking studies. Biotechniques 1998; 24:642–646, 648–651.
Frank JA, Zywicke H, Jordan EK, Mitchell J, Lewis BK, Miller B, Bryant H, Bulte JWM. 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 (Suppl 2):S484–S487.
Bulte JWM, Douglas T, Witwer B, Zhang S-C, Strable E, Lewis BK, Zywicke H, Miller B, van Gelderen P, Moskowitz BM, Duncan ID, Frank JA. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 2001; 19:1141–1147.
Josephson L, Tung C-H, Moore A, Weissleder R. High-efficiency intracellular magnetic labeling with novel superparamagnetic Tat peptide conjugates. Bioconjugate Chem 1999; 10:186–191.
Lewin M, Carlesso N, Tung C-H, Tang X-W, Cory D, Scadden DT, Weissleder R. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 2000; 18:410–414.
Kresse M, Wagner S, Pfefferer D, Lawaczeck R, Elste V, Semmler W. Targeting of ultrasmall superparamagnetic iron oxide (USPIO) particles to tumor cells in vivo by using transferrin receptor pathways. Magn Reson Med 1998; 40:236–242.
Okabe S, Forsberg-Nilsson K, Spiro AC, Segal M, McKay RDG. Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cell in vitro. Mech Dev 1996; 59:89–102.
Fraichard A, Chassande O, Bilbaut G, Dehay C, Savatier P, Samarut J. In vitro differentiation of embryonic stem cells into glial cells and functional neurons. J Cell Sci 1995; 108:3181–3188.
Hancock CR, Wetherington JP, Lambert NA, Condie BG. Neuronal differentiation of cryopreserved neural progenitor cells derived from mouse embryonic stem cells. Biochem Biophys Res Commun 2000; 271:418–421.
Daldrup-Link HE, Rudelius M, Oostendorp RAJ, Settles M, Piontek G, Rosenbrock X, Rummeny E, Schlegel J, Link T. Targeting of hematopoietic progenitor cells with MR contrast agents. Radiology 2003 (in press).
In den Kleef JJE, Cuppen JJM. RLSQ T1,T2 and ρ calculations, combining ratios and least squares. Magn Reson Med 1987; 5:513–524.
Malone RW, Felgner PL, Verma IM. Cationic liposome-mediated RNA transfection. Proc Natl Acad Sci U S A 1989; 86:6077–6081.
Chen CA, Okayama H. Calcium phosphate-mediated gene transfer: a highly efficient transfection system for stably transforming cells with plasmid DNA. Biotechniques 1988; 6:632–638.
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Rudelius, M., Daldrup-Link, H.E., Heinzmann, U. et al. Highly efficient paramagnetic labelling of embryonic and neuronal stem cells. Eur J Nucl Med Mol Imaging 30, 1038–1044 (2003). https://doi.org/10.1007/s00259-002-1110-0
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DOI: https://doi.org/10.1007/s00259-002-1110-0