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Multimodal Gadolinium Oxysulfide Nanoparticles: a Versatile Contrast Agent for Mesenchymal Stem Cell Labeling

Abstract

Despite a clear development of innovative therapies based on stem cells manipulation, the availability of new tools to better understand and follow stem cells behavior and improve their biomedical applications is not adequate. Indeed, an ideal tracking device must have a good ability to label stem cells as well as a complete neutrality relative to their biology. Furthermore, preclinical studies imply in vitro and in vivo approaches that often require several kinds of labeling and/or detection. Consequently, the multimodality concept presented in this work, may represent the solution to this problem as it has the potential to combine complementary imaging techniques. Spherical europium-doped gadolinium oxysulfide (Gd2O2S:Eu3+) nanoparticles are presented as a candidate as they are detectable by 1) magnetic resonance (MRI), 2) X-ray and 3) photoluminescence imaging. Whole body in vivo distribution, elimination and toxicity evaluation revealed a high tolerance of nanoparticles with a long-lasting MRI signal and a slow hepatobiliary and renal clearance. In vitro labeling of a wide variety of cells unveils the nanoparticles potential for efficient and universal cell tracking. Emphasis on mesenchymal stromal cells (MSCs) leads to the definition of optimal conditions for labeling and tracking in a context of cell therapy: concentrations below 50 µg mL-1 and diameters comprised between 170 and 300 nm. Viability, proliferation, migration and differentiation towards mesodermal lineages are preserved with these conditions and cell labeling appears to be persistent and without any leakage. Ex vivo detection of as few as two thousand five hundred Gd2O2S:Eu3+-labeled MSCs by MRI combined with in vitro examination with fluorescence microscopy highlights the feasibility of cell tracking in cell therapy using this new nanoplatform.

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Supplementary files

Publication details

The article was received on 20 Apr 2018, accepted on 05 Aug 2018 and first published on 10 Aug 2018


Article type: Paper
DOI: 10.1039/C8NR03263G
Citation: Nanoscale, 2018, Accepted Manuscript
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    Multimodal Gadolinium Oxysulfide Nanoparticles: a Versatile Contrast Agent for Mesenchymal Stem Cell Labeling

    J. Santelli, S. Lechevallier, H. Baaziz, M. Vincent, C. Martinez, R. MAURICOT, A. Parini, M. Verelst and D. Cussac, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C8NR03263G

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