Bifunctional Eu(3+)-doped Gd(2)O(3) nanoparticles as a luminescent and T(1) contrast agent for stem cell labeling

Magnetic resonance tracking of stem cells has recently become an emerging application for investigating cell-tissue interactions and guiding the development of effective stem cell therapies for regeneration of damaged tissues and organs. In this work, anionic Eu(3+)-doped Gd(2)O(3) hybrid nanoparticles were applied as a contrast agent both for fluorescence microscopy and T(1)-weighted MRI. The nanoparticles were synthesized through the polyol method and further modified with citric acid to obtain anionic nanoparticles. These nanoparticles were internalized into human mesenchymal stem cells (hMSCs) as confirmed by confocal laser scanning microscopy and quantified by inductively coupled plasma-mass spectrometry. MTT assay of the labeled cells showed that the nanoparticles did not possess significant cytotoxicity. In addition, the osteogenic, adipogenic and chondrogenic differentiation of the hMSCs was not influenced by the labeling process. With MRI, the in vitro detection threshold of cells after incubation with nanoparticles at a Gd concentration of 0.5 mM for 2 h was estimated to be about 10 000 cells. The results from this study indicate that the biocompatible anionic Gd(2)O(3) nanoparticles doped with Eu(3+) show promise both as a luminescent and T(1) contrast agent for use in visualizing hMSCs.