Variability in contrast agent uptake by different but similar stem cell types

• Published in: International journal of nanomedicine Vol. 8; no. 1; pp. 4577 - 4591
• Main Authors: Ketkar-Atre, Ashwini, Struys, Tom, Soenen, Stefaan J, Lambrichts, Ivo, Verfaillie, Catherine M, De Cuyper, Marcel, Himmelreich, Uwe
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2013; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Animals; Bone marrow; cell labeling; Cell Proliferation - drug effects; Contrast agents; Contrast media; Contrast Media - chemistry; Contrast Media - pharmacokinetics; Contrast Media - pharmacology; Health aspects; Humans; iron oxide; magnetic resonance imaging; Magnetic Resonance Imaging - methods; Magnetite Nanoparticles - chemistry; mesenchymal stem cells; Mice; MR contrast agents; multipotent adult progenitor cells; nanoparticles; NMR; Nuclear magnetic resonance; Original Research; Physiological aspects; Rats; Staining and Labeling; Stem cells; Stem Cells - chemistry; Stem Cells - cytology; Stem Cells - metabolism; transmission electron microscopy; Belgium; MR contrast agents; iron oxide; magnetic resonance imaging; cell labeling; nanoparticles; mesenchymal stem cells; transmission electron microscopy; multipotent adult progenitor cells
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S51588

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®, 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.