Variability in contrast agent uptake by different but similar stem cell types
The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI) contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP)-specific parameters. Here, we have studied three different types of NPs (Endorem (R), magnetoliposomes [MLs], and citrate coated C-200) to label relatively larger, mesenchymal stem cells (MSCs) and, much smaller yet faster proliferating, multipotent adult progenitor cells (MAPCs). Both cell types are similar, as they are isolated from bone marrow and have substantial regenerative potential, which make them interesting candidates for comparative experiments. Using NPs with different surface coatings and sizes, we found that differences in the proliferative and morphological characteristics of the cells used in the study are mainly responsible for the fate of endocytosed iron, intracellular iron concentration, and cytotoxic responses. The quantitative analysis, using high-resolution electron microscopy images, demonstrated a strong relationship between cell volume/surface, uptake, and cytotoxicity. Interestingly, uptake and toxicity trends are reversed if intracellular concentrations, and not amounts, are considered. This indicates that more attention should be paid to cellular parameters such as cell size and proliferation rate in comparative cell-labeling studies. ; The authors are grateful to Guerbet, Roissy, France, for the generous gift of Endorem (R). The technical assistance of Marc Jans, Manja Muitjens, and Pieter Berckmans is gratefully acknowledged. We would like to thank Jesse Trekker for the assistance with ICP-OES measurements. This work was financially supported by the European commission project EC-FP7-NMP-2008-Large 'ViBRANT' (228933), the Flemish Government for the SBO-IWT-80017 'iMAGiNe' and the SBO-IWT-060838 'BRAINSTIM', and by the KU Leuven Program Financing 'IMIR'. AKA is grateful for receiving financial support for a PhD fellowship (DBOF) from the KU Leuven.