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 microg 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 beta-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.

In vivo tracking of genetically engineered, anti-HER2/neu directed natural killer cells to HER2/neu positive mammary tumors with magnetic resonance imaging

“…In previous studies, we investigated the function of hematopoietic cells more extensively and did not find any impairment of the cells due to our labeling procedure (26,39). This is in accordance with data from the literature (17,20,22,25,(40)(41)(42). The migration properties of our cells were apparently not impaired, otherwise they had not reached the tumor tissue after intravenous administration.…”

In vivo cellular imaging of lymphocyte trafficking by MRI: A tumor model approach to cell‐based anticancer therapy

“…The use of an HIV-1 transactivator (Tat) peptide sequence, for example, can increase their uptake by lymphocytes more than 100-fold compared to untagged nanoparticles (21,22), permitting in vivo tracking of labeled cells (23)(24)(25). Other approaches to increase cellular uptake include receptor-mediated endocytosis, the use of carrier transporters as magnetodendrimers (26,27), and transfection methods combined with simple incubation (28,29).…”

The Myelin Mutants as Models to Study Myelin Repair in the Leukodystrophies

“…This has been demonstrated both ex vivo and in vivo in the md rat and migrations of cells followed longitudinally in the les rat spinal cord [86,87]. Neural stem cells induced to over-express Olig-2, which were derived from a luciferase-GFP-actin transgenic mouse and transplanted into a mouse fed cuprizone, were detected by bioluminescence imaging in the brain of live mice [88].…”