Transferrin Receptor Upregulation: In Vitro Labeling of Rat Mesenchymal Stem Cells with Superparamagnetic Iron Oxide

Schäfer, Richard; Kehlbach, Rainer; Wiskirchen, Jakub; Bantleon, Rüdiger; Pintaske, Jörg; Brehm, Bernhard R.; Gerber, Annika; Wolburg, Hartwig; Claussen, Claus D.; Northoff, Hinnak

doi:10.1148/radiol.2442060599

Cited by 100 publications

(89 citation statements)

References 38 publications

(45 reference statements)

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“…Clinical translation of ex vivo-labeling procedures is complicated from a regulatory point of view, as these manipulations greatly enhance the risk of cell sample contamination (24), alterations in stem cell biology, or in vivo side effects from added transfection agents (25)(26)(27) (28). In addition, some ultrasmall superparamagnetic iron oxide-transfection agent combinations have induced cytotoxic effects (29)(30)(31)(32) or altered the stem cell biology (33). To avoid these complications, we undertook to determine whether an immediately clinically applicable approach for stem cell labeling, which would not require ex vivo manipulations of harvested cells and which would eliminate the need for transfection agents, could be used to track transplanted MSCs.…”

Section: Methodsmentioning

confidence: 99%

Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation

Khurana¹,

Chapelin²,

Beck³

et al. 2013

Radiology

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Purpose:To determine whether intravenous ferumoxytol can be used to effectively label mesenchymal stem cells (MSCs) in vivo and can be used for tracking of stem cell transplants. Materials and Methods:This study was approved by the institutional animal care and use committee. Sprague-Dawley rats (6-8 weeks old) were injected with ferumoxytol 48 hours prior to extraction of MSCs from bone marrow. Ferumoxytol uptake by these MSCs was evaluated with fluorescence, confocal, and electron microscopy and compared with results of traditional ex vivo-labeling procedures. The in vivo-labeled cells were subsequently transplanted in osteochondral defects of 14 knees of seven athymic rats and were evaluated with magnetic resonance (MR) imaging up to 4 weeks after transplantation. T2 relaxation times of in vivo-labeled MSC transplants and unlabeled control transplants were compared by using t tests. MR data were correlated with histopathologic results. Results:In vivo-labeled MSCs demonstrated significantly higher ferumoxytol uptake compared with ex vivo-labeled cells. With electron microscopy, iron oxide nanoparticles were localized in secondary lysosomes. In vivo-labeled cells demonstrated significant T2 shortening effects in vitro and in vivo when they were compared with unlabeled control cells (T2 in vivo, 15.4 vs 24.4 msec; P , .05) and could be tracked in osteochondral defects for 4 weeks. Histologic examination confirmed the presence of iron in labeled transplants and defect remodeling. Conclusion:Intravenous ferumoxytol can be used to effectively label MSCs in vivo and can be used for tracking of stem cell transplants with MR imaging. This method eliminates risks of contamination and biologic alteration of MSCs associated with ex vivo-labeling procedures.q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl

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Section: Methodsmentioning

confidence: 99%

Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation

Khurana¹,

Chapelin²,

Beck³

et al. 2013

Radiology

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“…It has been able to be shown experimentally in vitro that polymer-coated SPIO (PEG/dextran-SPIO) only have a minimal effect on cell function and vitality [54]. However, newer studies show that internalized SPIO can influence the cell expression pattern (e. g. by oxidative stress), cell proliferation, and cell differentiation [55]. Methods for core labeling (e. g. 59 Fe [56]) and coating labeling with radioisotopes [57] (e. g. 111 In [61].…”

Section: Distribution Degradation and Toxicitymentioning

confidence: 99%

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Ittrich¹,

Peldschus²,

Raabe³

et al. 2013

Fortschr Röntgenstr

124

101

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Superparamagnetic iron oxide nanoparticles (SPIO) can be used to image physiological processes and anatomical, cellular and molecular changes in diseases. The clinical applications range from the imaging of tumors and metastases in the liver, spleen and bone marrow, the imaging of lymph nodes and the CNS, MRA and perfusion imaging to atherosclerotic plaque and thrombosis imaging. New experimental approaches in molecular imaging describe undirected SPIO trapping (passive targeting) in inflammation, tumors and associated macrophages as well as the directed accumulation of SPIO ligands (active targeting) in tumor endothelia and tumor cells, areas of apoptosis, infarction, inflammation and degeneration in cardiovascular and neurological diseases, in atherosclerotic plaques or thrombi. The labeling of stem or immune cells allows the visualization of cell therapies or transplant rejections. The coupling of SPIO to ligands, radio- and/or chemotherapeutics, embedding in carrier systems or activatable smart sensor probes and their externally controlled focusing (physical targeting) enable molecular tumor therapies or the imaging of metabolic and enzymatic processes. Monodisperse SPIO with defined physicochemical and pharmacodynamic properties may improve SPIO-based MRI in the future and as targeted probes in diagnostic magnetic resonance (DMR) using chip-based ?NMR may significantly expand the spectrum of in vitro analysis methods for biomarker, pathogens and tumor cells. Magnetic particle imaging (MPI) as a new imaging modality offers new applications for SPIO in cardiovascular, oncological, cellular and molecular diagnostics and therapy. Key Points: Citation Format:

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“…This was done by using SPIO to label the cells, and detect ion was done by using Magnetic Resonance Imaging (MRI). The viability or differentiation potential of the cells has not been affected by SPIOlabelling of MSC [31], [32], but it has an impact on the iron metabolism, the migration capacity, and the colony formation of MSC [32]- [34]. The principle function of MRI is the exposure of cells to high MF and magnetic force that can direct the iron labelled stem cells in vitro and in vivo [35]- [37], guided localization of iron labelled stem cells to the desired region [35], [38], for the seeding of scaffolds with stem cells [36], [39], or for the engineering of 3D tissues by stem cells [37].…”

Section: Discussionmentioning

confidence: 99%

A Preliminary Study on Magnetic Fields Effects on Stem Cell Differentiation

Miskon

Uslama

2011

IFMBE Proceedings

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Abstract-The objective of this paper is to provide the fundamental mathematical formula to predict the effect of magnetic fields (MF) on stem cell differentiation. The data were reviewed from journals related to the effects of magnetic fields on stem cell differentiation. These data were given a value for differentiation which is related to their MF strength with these conditions; MF strength that does not affect the stem cell differentiation given the value of zero, MF strength that results in stem cells death given the value of 1, and the MF strength that affects stem cells The differentiation given the value between 0.1 and 0.9. graph was plotted according to these data and the mathematical equation is designed from the graph. From this review, we suggest that the intensity of MF that can affect the stem cell differentiation is between 600µT and 9.4T in which the cell differentiation will not occur with intensity of less than 10µT and intensity of more than 12T will cause the death of stem cells. We also suggest that the limit of MF effects on stem cell differentiation lies between 10 µT and 600 µT, and the limit of MF strength that can lead to the death of stem cells lies between 9.4 T and 12 T. It can be concluded that the exposure of MF on stem cell differentiation depends not only on the MF intensity, but also on the period of exposure.

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Transferrin Receptor Upregulation: In Vitro Labeling of Rat Mesenchymal Stem Cells with Superparamagnetic Iron Oxide

Abstract: SPIO or USPIO labeling without TAs has an influence on gene expression of MSCs upregulating transferrin receptor. Furthermore, SPIO labeling with a TA will coat the cellular surface.

Cited by 100 publications

References 38 publications

Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation

Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

A Preliminary Study on Magnetic Fields Effects on Stem Cell Differentiation

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