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

Magnetic resonance (MR) tracking of magnetically labeled stem and progenito r cells is an emerging technology, leading to an urgent need for magnetic p robes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnet ic 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) loc alization in endosomes. The superparamagnetic iron oxide nanocomposites hav e been optimized to exhibit superior magnetic properties and to induce suff icient MR cell contrast at incubated doses as low as 1 mug iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibi t an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as hig h as 24-39 s(-1)/mM iron. Labeled cells are unaffected in their viability a nd proliferating capacity, and labeled human NSCs differentiate normally in to neurons. Furthermore, we show here that NSC-derived (and LacZ-transfecte d), magnetically labeled oligodendroglial progenitors can be readily detect ed in vivo at least as long as six weeks after transplantation, with an exc ellent correlation between the obtained MR contrast and staining for beta - galactosidase expression. The availability of magnetodendrimers opens up th e possibility of MR tracking of a wide variety of (stem) cell transplants.