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

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 ne...

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Main Authors: Ariza de Schellenberger, Angela, Kratz, Harald, Farr, Tracy D., Löewa, Norbert, Hauptmann, Ralf, Wagner, Susanne, Taupitz, Matthias, Schnorr, Jörg, Schellenberger, Eyk A.
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Published: Dove Medical Press 2016
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Online Access:https://eprints.nottingham.ac.uk/32791/
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author Ariza de Schellenberger, Angela
Kratz, Harald
Farr, Tracy D.
Löewa, Norbert
Hauptmann, Ralf
Wagner, Susanne
Taupitz, Matthias
Schnorr, Jörg
Schellenberger, Eyk A.
author_facet Ariza de Schellenberger, Angela
Kratz, Harald
Farr, Tracy D.
Löewa, Norbert
Hauptmann, Ralf
Wagner, Susanne
Taupitz, Matthias
Schnorr, Jörg
Schellenberger, Eyk A.
author_sort Ariza de Schellenberger, Angela
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-327912020-05-04T17:46:55Z https://eprints.nottingham.ac.uk/32791/ Labeling of mesenchymal stem cells for MRI with single-cell sensitivity Ariza de Schellenberger, Angela Kratz, Harald Farr, Tracy D. Löewa, Norbert Hauptmann, Ralf Wagner, Susanne Taupitz, Matthias Schnorr, Jörg Schellenberger, Eyk A. 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. Dove Medical Press 2016-04-12 Article PeerReviewed Ariza de Schellenberger, Angela, Kratz, Harald, Farr, Tracy D., Löewa, Norbert, Hauptmann, Ralf, Wagner, Susanne, Taupitz, Matthias, Schnorr, Jörg and Schellenberger, Eyk A. (2016) Labeling of mesenchymal stem cells for MRI with single-cell sensitivity. International Journal of Nanomedicine, 11 . pp. 1517-1535. ISSN 1178-2013 Magnetic field microdistortions Single-cell imaging Mesenchymal stem cells VSOP MCP Resovist® http://dx.doi.org/10.2147/IJN.S101141 doi:10.2147/IJN.S101141 doi:10.2147/IJN.S101141
spellingShingle Magnetic field microdistortions
Single-cell imaging
Mesenchymal stem cells
VSOP
MCP
Resovist®
Ariza de Schellenberger, Angela
Kratz, Harald
Farr, Tracy D.
Löewa, Norbert
Hauptmann, Ralf
Wagner, Susanne
Taupitz, Matthias
Schnorr, Jörg
Schellenberger, Eyk A.
Labeling of mesenchymal stem cells for MRI with single-cell sensitivity
title 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_short Labeling of mesenchymal stem cells for MRI with single-cell sensitivity
title_sort labeling of mesenchymal stem cells for mri with single-cell sensitivity
topic Magnetic field microdistortions
Single-cell imaging
Mesenchymal stem cells
VSOP
MCP
Resovist®
url https://eprints.nottingham.ac.uk/32791/
https://eprints.nottingham.ac.uk/32791/
https://eprints.nottingham.ac.uk/32791/