In vivo MRI mapping of iron oxide-labeled stem cells transplanted in the heart

In various stem cell therapy approaches poor cell survival has been recognized as an important factor limiting therapeutic efficacy. Therefore noninvasive monitoring of cell fate is warranted for developing clinically effective stem cell therapy. In this study we investigated the use of voxel-based R₂ mapping as a tool to monitor the fate of iron oxide-labeled cells in the myocardium. Mesenchymal stem cells were transduced with the luciferase gene, labeled with ferumoxide particles and injected in the myocardium of healthy rats. Cell fate was monitored over a period of 8 weeks by bioluminescence and quantitative magnetic resonance imaging. Bioluminescence signal increased during the first week followed by a steep decrease to undetectable levels during the second week. MR imaging showed a sharp increase in R₂ values shortly after injection at the injection site, followed by a very gradual decrease of R₂ over a period of 8 weeks. No difference in the appearances on R₂-weighted images was observed between living and dead cells over the entire time period studied. No significant correlation between the bioluminescence optical data and R₂ values was observed and quantitative R₂ mapping appeared not suitable for the in vivo assessment of stem cell. These results do not follow previous in vitro reports where it was proposed that living cells may be distinguished from dead cells on the basis of the R₂ relaxivities (intracellular and extracellular iron oxides). Cell proliferation, cell migration, cell death, extracellular superparamagnetic iron oxide dispersion and aggregation exhibit different relaxivities. In vivo these processes happen simultaneously, making quantification very complex, if not impossible.