Use of ferumoxides for stem cell labeling

Aim: Although numerous clinical trials have shown promising results with regards to the cardiac regenerative capacity of different types of stem cells, there remains virtually no evidence of the fate of stem cells in these human studies, primarily owing to safety concerns associated with the use of cell-labeling strategies. Methods: In this study, we utilized two cell types that are used extensively in cardiac regeneration studies, namely bone marrow-derived human mononuclear cells and C2C12 skeletal myoblasts. The US FDA-approved compounds feridex (ferumoxide) and protamine sulfate (as a transfection agent) were used in combination for cellular labeling. We assessed the effect of this cell labeling strategy on cellular viability, proliferation and differentiation both in vitro and in vivo. Results: The ferumoxide-protamine sulfate combination had no effect on cellular viability, proliferation or differentiation. We show that the labeled human mononuclear cells were easily identified within the rat myocardium 1 month following injection into the myocardium. These human cells expressed human-specific cardiac troponin 1, whereas the neighboring rat myocardium did not. Furthermore, we demonstrated that this labeling strategy can be used with high accuracy for magnetic separation of the labeled cells based on the intracellular ferumoxide particles. Conclusions: The ferumoxide-protamine sulfate combination can be used safely and effectively to enhance the detection and isolation of cardiogenic stem cell populations.