Labeling of mesenchymal stem cells for MRI with single-cell sensitivity
Angela Ariza de Schellenberger,1 Harald Kratz,1 Tracy D Farr,2,3 Norbert Löwa,4 Ralf Hauptmann,1 Susanne Wagner,1 Matthias Taupitz,1 Jörg Schnorr,1 Eyk A Schellenberger1 1Department of Radiology, 2Department of Experimental Neurology, Center for Stroke Research Berlin, Charit&...
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Dove Medical Press
2016
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oai:doaj.org-article:013f6f4eb13e408f8ddef024fd1d71ed2021-12-02T01:41:25ZLabeling of mesenchymal stem cells for MRI with single-cell sensitivity1178-2013https://doaj.org/article/013f6f4eb13e408f8ddef024fd1d71ed2016-04-01T00:00:00Zhttps://www.dovepress.com/labeling-of-mesenchymal-stem-cells-for-mri-with-single-cell-sensitivit-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Angela Ariza de Schellenberger,1 Harald Kratz,1 Tracy D Farr,2,3 Norbert Löwa,4 Ralf Hauptmann,1 Susanne Wagner,1 Matthias Taupitz,1 Jörg Schnorr,1 Eyk A Schellenberger1 1Department of Radiology, 2Department of Experimental Neurology, Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany; 3School of Life Sciences, University of Nottingham, Medical School, Nottingham, UK; 4Department of Biomagnetic Signals, Physikalisch-Technische Bundesanstalt Berlin, Berlin, Germany 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. Keywords: magnetic field microdistortions, single-cell imaging, mesenchymal stem cells, VSOP, MCP, Resovist®Ariza de Schellenberger AKratz HFarr TDLöwa NHauptmann RWagner STaupitz MSchnorr JSchellenberger EADove Medical PressarticleMagnetic field micro distortionsSingle cell imagingMesenchymal stem cellsVSOPMCPResovistMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1517-1535 (2016) |
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Magnetic field micro distortions Single cell imaging Mesenchymal stem cells VSOP MCP Resovist Medicine (General) R5-920 |
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Magnetic field micro distortions Single cell imaging Mesenchymal stem cells VSOP MCP Resovist Medicine (General) R5-920 Ariza de Schellenberger A Kratz H Farr TD Löwa N Hauptmann R Wagner S Taupitz M Schnorr J Schellenberger EA Labeling of mesenchymal stem cells for MRI with single-cell sensitivity |
description |
Angela Ariza de Schellenberger,1 Harald Kratz,1 Tracy D Farr,2,3 Norbert Löwa,4 Ralf Hauptmann,1 Susanne Wagner,1 Matthias Taupitz,1 Jörg Schnorr,1 Eyk A Schellenberger1 1Department of Radiology, 2Department of Experimental Neurology, Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany; 3School of Life Sciences, University of Nottingham, Medical School, Nottingham, UK; 4Department of Biomagnetic Signals, Physikalisch-Technische Bundesanstalt Berlin, Berlin, Germany 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. Keywords: magnetic field microdistortions, single-cell imaging, mesenchymal stem cells, VSOP, MCP, Resovist® |
format |
article |
author |
Ariza de Schellenberger A Kratz H Farr TD Löwa N Hauptmann R Wagner S Taupitz M Schnorr J Schellenberger EA |
author_facet |
Ariza de Schellenberger A Kratz H Farr TD Löwa N Hauptmann R Wagner S Taupitz M Schnorr J Schellenberger EA |
author_sort |
Ariza de Schellenberger A |
title |
Labeling of mesenchymal stem cells for MRI with single-cell sensitivity |
title_short |
Labeling of mesenchymal stem cells for MRI with single-cell sensitivity |
title_full |
Labeling of mesenchymal stem cells for MRI with single-cell sensitivity |
title_fullStr |
Labeling of mesenchymal stem cells for MRI with single-cell sensitivity |
title_full_unstemmed |
Labeling of mesenchymal stem cells for MRI with single-cell sensitivity |
title_sort |
labeling of mesenchymal stem cells for mri with single-cell sensitivity |
publisher |
Dove Medical Press |
publishDate |
2016 |
url |
https://doaj.org/article/013f6f4eb13e408f8ddef024fd1d71ed |
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