Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

Ariza de Schellenberger, Angela; Kratz, Harald; Farr, Tracy D.; L�ewa, Norbert; Hauptmann, Ralf; Wagner, Susanne; Taupitz, Matthias; Schnorr, J�rg; Schellenberger, Eyk A.

Abstract

Sensitive cell detection by magnetic resonance imaging (MRI) is an important tool for the development of cell therapies. However, clinically approved contrast agents that allow single-cell detection are currently not available. Therefore, we compared very small iron oxide nanoparticles (VSOP) and new multicore carboxymethyl dextran-coated iron oxide nanoparticles (multicore particles, MCP) designed by our department for magnetic particle imaging (MPI) with discontinued Resovist® regarding their suitability for detection of single mesenchymal stem cells (MSC) by MRI. We achieved an average intracellular nanoparticle (NP) load of .10 pg Fe per cell without the use of transfection agents. NP loading did not lead to significantly different results in proliferation, colony formation, and multilineage in vitro differentiation assays in comparison to controls. MRI allowed single-cell detection using VSOP, MCP, and Resovist® in conjunction with high-resolution T2*-weighted imaging at 7 T with postprocessing of phase images in agarose cell phantoms and in vivo after delivery of 2,000 NP-labeled MSC into mouse brains via the left carotid artery. With optimized labeling conditions, a detection rate of ~45% was achieved; however, the experiments were limited by nonhomogeneous NP loading of the MSC population. Attempts should be made to achieve better cell separation for homogeneous NP loading and to thus improve NP-uptake-dependent biocompatibility studies and cell detection by MRI and future MPI. Additionally, using a 7 T MR imager equipped with a cryocoil resulted in approximately two times higher detection. In conclusion, we established labeling conditions for new high-relaxivity MCP, VSOP, and Resovist® for improved MRI of MSC with single-cell sensitivity.

Citation

Ariza de Schellenberger, A., Kratz, H., Farr, T. D., Löewa, N., Hauptmann, R., Wagner, S., …Schellenberger, E. A. (2016). Labeling of mesenchymal stem cells for MRI with single-cell sensitivity. International Journal of Nanomedicine, 11, 1517-1535. https://doi.org/10.2147/IJN.S101141

• Journal Article Type: Article
• Acceptance Date: Jan 29, 2016
• Publication Date: Apr 12, 2016
• Deposit Date: Apr 15, 2016
• Publicly Available Date: Apr 15, 2016
• Journal: International Journal of Nanomedicine
• Print ISSN: 1176-9114
• Electronic ISSN: 1178-2013
• Publisher: Dove Medical Press
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Pages: 1517-1535
• DOI: https://doi.org/10.2147/IJN.S101141
• Keywords: Magnetic field microdistortions, Single-cell imaging, Mesenchymal stem cells, VSOP, MCP, Resovist®
• Public URL: https://nottingham-repository.worktribe.com/output/785491
• Publisher URL: http://dx.doi.org/10.2147/IJN.S101141
• Additional Information: Originally published in International Journal of Nanomedicine by Dove Medical Press