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Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells

Abstract

Magnetic 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 μg 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 β-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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Acknowledgements

We are indebted to John Colen and Brett Worly for their help with cell labeling and imaging; Jonathan Hill and Glenn Walter for providing the 3T3 and C2C12 cells, respectively; Neuralstem Biopharmaceuticals and Karl Johe for providing the human NSCs and Jacquie Shukaliah for helpful discussions. This work was partially supported by a grant from the National Science Foundation (NSF) to T.D. (CHE-9801685) and the Oscar Rennebohm Foundation to I.D.D. The Institute for Rock Magnetism is supported by grants from the Keck Foundation and NSF.

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Bulte, J., Douglas, T., Witwer, B. et al. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 19, 1141–1147 (2001). https://doi.org/10.1038/nbt1201-1141

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