Page 31 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

1 Introduction
Cell-based therapy approaches are currently receiving a lot of attention for regenerative medicine purposes (1). In order to assess the clinical value and safety of cell therapy approaches, it is necessary to track the fate of the transplanted cells in vivo. For in vivo cell tracking it is essential that the cells have incorporated a label in order to distinguish them from their surroundings in MR images (2–5). The easiest way to label a cell is to add the label to the culture medium. To improve uptake efficiency, a transfection agent can be used (5). In labeling of cells some aspects have to be considered:
(1) the efficiency of the labeling procedure;
(2) the effect of labeling on cell survival;
(3) the behavior of the label in the cell;
(4) the duration of label retention in the cell;
(5) preservation of cell function and surface marker expression.
For cell tracking by MRI different labels can be used (1,6,7). Iron-oxide nanoparticles are, however, the most commonly used labels, and were even shown to allow for detection of single cells in vivo (8). A vast amount of studies have been published dealing with labeling of various cell types with iron oxide nanoparticles (9–11). In these studies a large variety of labeling protocols have been described (12–14). While for every cell type tested efficient labeling and subsequent detection by MRI has been reported, it is not clear how different labeling protocols may influence labeling efficiency. Various studies have shown effects of particle coating, particle size, labeling dose and labeling time on labeling efficiency and the ability to detect labeled cells by MRI (15–18). The purpose of this study was to systematically investigate the effect of variations in dose and duration of labeling on label incorporation, distribution, retention and toxicity using two commonly applied types of iron oxide nanoparticles – the so-called SPIO (super paramagnetic iron oxide particles) and MPIO (micro particles of iron oxide) particles. Of these two, the most widely used are SPIO particles, which have a particle diameter between 80 and 150 nm, consisting of an iron oxide core (Fe2O3 and Fe3O4 crystals) of 4 nm with a low-molecular-weight dextran coating (19–23). MPIO particles are composed of polystyrene–divinyl benzene polymer micro spheres containing a magnetite core and are tagged with the fluorescent dye Dragon
Influence of SPIO cell labeling protocol
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