Recently, debate has arisen about the usefulness of cell tracking using iron oxide-labeled cells. Two important issues in determining the usefulness of cell tracking with MRI are generally overlooked; first, the effect of graft rejection in immunocompetent models, and second, the necessity for careful histological confirmation of the fate of the labeled cells in the presence of iron oxide. Therefore, both iron oxide-labeled living as well as dead epicardium-derived cells (EPDCs) were investigated in ischemic myocardium of immunodeficient non-obese diabetic (NOD)/acid: non-obese diabetic severe combined immunodeficient (NOD/scid) mice with 9.4T MRI until 6 weeks after surgery, at which time immunohistochemical analysis was performed. In both groups, voids on MRI scans were observed that did not change in number, size, or localization over time. Several studies demonstrated that iron-labeled cellular transplants were visible with MRI and could be followed over time (3,4,6,7), even when a magnet of clinical field strength was used (4,8), although the detection limit was low and only high numbers of iron-loaded cells were visible (9). It was only assumed that these hypointense spots on the MRI images actually represented the transplanted living iron-loaded cells. It was not verified whether the transplanted cells were indeed present in histological sections, and whether MRI signal was really generated by the original transplant and not by, e.g., macrophages that had phagocytosed the iron-containing cells. The first study (5) that addressed this issue reported that the MRI signal originally generated by iron in transplanted MSCs appeared to be present regardless of the existence of these cells, which was later confirmed by Terrovitis et al. (10), who demonstrated, like Amsalem et al. (5) had done before, that iron-loaded macrophages created the signal rather than the iron-loaded living transplanted cells.As suggested by Sadek and Garry (11) in a comment on the study of Amsalem et al. (5), the results should be extended by studies in immunocompromised animals. In the previous studies, cardiac-derived stem cells (CDCs) or MSCs, which are not immunoprivileged, were harvested from "syngeneic" rats and transplanted into other inbred immunocompetent rats (5,10). However, rats cannot, unlike mouse donors from same inbred strain, be considered really syngeneic but rather allogeneic (5), implying that the cells could simply be rejected by the host, and thus that the concern regarding the utility of SPIOs in cardiac cell therapy applies only to comparable studies with nonautologous cells and immunocompetent animals. Sadek and Garry (11), therefore, pleaded for similar experiments with either autologous cell transplantation in normal animals, or with allogeneic stem cell transplantation into immunodeficient animals (11). It could very well be that iron-loaded transplanted cells are not rejected in those settings or that the clearance pattern is altered in such a way that the hypointense signals from iron-oxide largely correspon...