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

Ariza de Schellenberger A, Kratz H, Farr TD, Löwa N, Hauptmann R, Wagner S, Taupitz M, Schnorr J, Schellenberger EA - Int J Nanomedicine (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Center for Stroke Research Berlin, Charité - Universitätsmedizin 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.

No MeSH data available.


Related in: MedlinePlus

MRI quantification of single cells in agarose phantoms and correlation with intracellular iron content for cells labeled with Resovist®, MCP, and VSOP.Notes: Increasing iron uptake correlates with increasing MRI detection (mean; bars, ± SD; n=4) for single cells. VSOP-MSC average detection increased from 14% (4 pg Fe per cell) to 43% (21 pg Fe per cell). Resovist®-MSC average detection increased from 28% (9.2 pg Fe per cell) to 44% (13 pg Fe per cell) and MCP-MSC detection from 28% (6 pg Fe per cell) to 45% (17 pg Fe per cell).Abbreviations: MCP, multicore carboxy-methyl-dextran-coated iron oxide nanoparticle; MRI, magnetic resonance imaging, MSC, mesenchymal stem cells; VSOP, very small iron oxide nanoparticle.
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f5-ijn-11-1517: MRI quantification of single cells in agarose phantoms and correlation with intracellular iron content for cells labeled with Resovist®, MCP, and VSOP.Notes: Increasing iron uptake correlates with increasing MRI detection (mean; bars, ± SD; n=4) for single cells. VSOP-MSC average detection increased from 14% (4 pg Fe per cell) to 43% (21 pg Fe per cell). Resovist®-MSC average detection increased from 28% (9.2 pg Fe per cell) to 44% (13 pg Fe per cell) and MCP-MSC detection from 28% (6 pg Fe per cell) to 45% (17 pg Fe per cell).Abbreviations: MCP, multicore carboxy-methyl-dextran-coated iron oxide nanoparticle; MRI, magnetic resonance imaging, MSC, mesenchymal stem cells; VSOP, very small iron oxide nanoparticle.

Mentions: A correlation between the average NP uptake per cell and the number of detected cells by MRI was used to determine the sensitivity of the 7 T Pharmascan setting used in our experiments (Figure 5).


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

Ariza de Schellenberger A, Kratz H, Farr TD, Löwa N, Hauptmann R, Wagner S, Taupitz M, Schnorr J, Schellenberger EA - Int J Nanomedicine (2016)

MRI quantification of single cells in agarose phantoms and correlation with intracellular iron content for cells labeled with Resovist®, MCP, and VSOP.Notes: Increasing iron uptake correlates with increasing MRI detection (mean; bars, ± SD; n=4) for single cells. VSOP-MSC average detection increased from 14% (4 pg Fe per cell) to 43% (21 pg Fe per cell). Resovist®-MSC average detection increased from 28% (9.2 pg Fe per cell) to 44% (13 pg Fe per cell) and MCP-MSC detection from 28% (6 pg Fe per cell) to 45% (17 pg Fe per cell).Abbreviations: MCP, multicore carboxy-methyl-dextran-coated iron oxide nanoparticle; MRI, magnetic resonance imaging, MSC, mesenchymal stem cells; VSOP, very small iron oxide nanoparticle.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835118&req=5

f5-ijn-11-1517: MRI quantification of single cells in agarose phantoms and correlation with intracellular iron content for cells labeled with Resovist®, MCP, and VSOP.Notes: Increasing iron uptake correlates with increasing MRI detection (mean; bars, ± SD; n=4) for single cells. VSOP-MSC average detection increased from 14% (4 pg Fe per cell) to 43% (21 pg Fe per cell). Resovist®-MSC average detection increased from 28% (9.2 pg Fe per cell) to 44% (13 pg Fe per cell) and MCP-MSC detection from 28% (6 pg Fe per cell) to 45% (17 pg Fe per cell).Abbreviations: MCP, multicore carboxy-methyl-dextran-coated iron oxide nanoparticle; MRI, magnetic resonance imaging, MSC, mesenchymal stem cells; VSOP, very small iron oxide nanoparticle.
Mentions: A correlation between the average NP uptake per cell and the number of detected cells by MRI was used to determine the sensitivity of the 7 T Pharmascan setting used in our experiments (Figure 5).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Center for Stroke Research Berlin, Charité - Universitätsmedizin 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.

No MeSH data available.


Related in: MedlinePlus