Nature Biotechnology
19, 1141 - 1147 (2001)
doi:10.1038/nbt1201-1141
Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cellsJeff W.M. Bulte1, 2, Trevor Douglas3, Brian Witwer4, Su-Chun Zhang4, Erica Strable3, Bobbi K. Lewis1, Holly Zywicke1, Brad Miller1, Peter van Gelderen5, Bruce M. Moskowitz6, Ian D. Duncan4
& Joseph A. Frank11
Laboratory of Diagnostic Radiology Research (CC), National Institutes of Health, Bethesda, MD 20892. 2
Current address: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2195. 3
Department of Chemistry, Temple University, Philadelphia, PA 19122. 4
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53705. 5
Advanced Magnetic Resonance Imaging (NINDS), National Institutes of Health, Bethesda, MD 20892. 6
Institute for Rock Magnetism, Department of Geology and Geophysics, University of Minnesota, Minneapolis, MN 55455.
Correspondence should be addressed to Jeff W.M. Bulte jwmbulte@mri.jhu.eduMagnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1  g iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24−39 s-1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for  -galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.
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