Nanoparticles as magnetic resonance imaging contrast agents. Feasibility studies on cell labelling, acute myocardial infarct imaging and articular cartilage imaging

Acute myocardial infarction and osteoarthritis are both diseases of tissues with poor regenerative capacities. Stem cell therapies administered post-infarction have shown therapeutic potential. With the previously used approaches, the engraftment of the cells in the myocardium has been low and the mechanisms behind the observed therapeutic effects are thought to involve multifactorial processes. It has been hypothesized that the earliest biochemical changes, mainly proteoglycan depletion of osteoarthritis, might be reversible. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage has been shown to be a sensitive way to assess proteoglycan depletion in osteoarthritis, however the use of gadolinium has now raised safety concerns.

Magnetic resonance imaging is currently the preferred method for assessing the label in a living tissue. Superparamagnetic iron oxide nanoparticles have shown some potential for stem cell labelling however there are interpretational challenges with the contrast and those labelling methods that are considered to be safe are time consuming.

The object of the present work was to develop labels and labelling methods for cellular magnetic resonance imaging. The usability of a novel fast rotation incubation labelling method for labelling bone marrow mononuclear cells and the evaluation of cell homing in an experimental acute myocardial infarct model were studied. The labelling method appeared to be feasible for acute phase cell tracking. The transplantation of the cells seemed to improve the ejection fraction at three weeks’ post-infarction.

Novel manganese oxide labels were developed to overcome the signal interpretational problems associated with the superparamagnetic iron oxide nanoparticle label. Amorphous manganese oxide was observed to have better relaxometric properties than crystalline manganese oxide, although both compounds appeared to be safe, high in relaxivity and suitable for cellular magnetic resonance imaging in vitro. The usability of the amorphous label in assessing the proteoglycan content in osteoarthritis was investigated. The relaxation of the label seemed higher than the corresponding phenomenon with gadolinium and the behavior of the label was observed to mimic that of delayed gadolinium-enhanced magnetic resonance imaging of cartilage.

In conclusion, both the novel fast labelling method and the novel label were demonstrated to be feasible and functional in these experimental models.