Ferumoxytol: A New, Clinically Applicable Label for Stem-Cell Tracking in Arthritic Joints with MRI

Khurana, Aman; Nejadnik, Hossein; Chapelin, Fanny; Lenkov, Olga; Gawande, Rakhee; Lee, Sung-Min; Gupta, Sandeep; Aflakian, Nooshin; Derugin, Nikita; Messing, Solomon; Lin, Guiting; Lue, Tom F.; Pisani, Laura; Daldrup-Link, Heike E.

doi:10.2217/nnm.12.198

Cited by 79 publications

(85 citation statements)

References 61 publications

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“…In this study, we present Labeling MSC with ferumoxytol (Feraheme ® ), as described by Thu et al 65 (average NP load with $2.2 pg Fe per cell), 65 was not successful in our hands and did not result in a significant NP load per cell. This poor uptake of ferumoxytol, as also the uptake reported by other authors, [28][29][30] might not be sufficient to achieve single-cell detection by MRI as discussed in this report. Therefore, we chose MCP, VSOP, and Resovist ® to accomplish single-cell detection by MRI.…”

Section: Discussionmentioning

confidence: 48%

“…To the best of our knowledge, the most sensitive MRI detection has been accomplished for 1,000 ferumoxytol-labeled cells after intracerebral implantation when cells were labeled with 2.2 pg Fe per cell. [27][28][29][30] However, no attempts have been made to visualize single cells with any of these approaches. Alternatively, Bulte 31 proposed in vivo labeling of MSC obtained by bone marrow (BM) aspiration from rats after prior IV injection with ferumoxytol.…”

Section: Introductionmentioning

confidence: 99%

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

Schellenberger¹,

Kratz²,

Farr³

et al. 2016

IJN

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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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Section: Discussionmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

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

Schellenberger¹,

Kratz²,

Farr³

et al. 2016

IJN

View full text Add to dashboard Cite

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“…56,60 Current strategies seem to be focused on off-label use of already FDA-approved components in generating a SPIO-based intracellular labelling agent. 56,61 The transfection agent poly-L-lysine was used to promote cellular uptake of the iron oxide nanoparticles. The transfection agent poly-L-lysine (Sigma, St Louis, MI) was used to promote cellular uptake of the iron oxide nanoparticles.…”

Section: Superparamagnetic Iron Oxide Nanoparticlesmentioning

confidence: 99%

Nanoparticles and clinically applicable cell tracking

Bernsen

Guenoun

Tiel

et al. 2015

BJR

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In vivo cell tracking has emerged as a much sought after tool for design and monitoring of cell-based treatment strategies. Various techniques are available for pre-clinical animal studies, from which much has been learned and still can be learned. However, there is also a need for clinically translatable techniques. Central to in vivo cell imaging is labelling of cells with agents that can give rise to signals in vivo, that can be detected and measured non-invasively. The current imaging technology of choice for clinical translation is MRI in combination with labelling of cells with magnetic agents. The main challenge encountered during the cell labelling procedure is to efficiently incorporate the label into the cell, such that the labelled cells can be imaged at high sensitivity for prolonged periods of time, without the labelling process affecting the functionality of the cells. In this respect, nanoparticles offer attractive features since their structure and chemical properties can be modified to facilitate cellular incorporation and because they can carry a high payload of the relevant label into cells. While these technologies have already been applied in clinical trials and have increased the understanding of cell-based therapy mechanism, many challenges are still faced.

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“…Recent studies, however, have shown that iron oxide labeling, combined with magnetic targeting, might improve graft retention in the rat heart [29,30,34,36]. Thus, ferumoxytol cell labeling might have utility in both in vivo cardiac graft imaging and cell retention.…”

confidence: 99%

Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

Skelton

Khoja

Almeida

et al. 2015

Stem Cells Translational Medicine

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Given the limited regenerative capacity of the heart, cellular therapy with stem cell-derived cardiac cells could be a potential treatment for patients with heart disease. However, reliable imaging techniques to longitudinally assess engraftment of the transplanted cells are scant. To address this issue, we used ferumoxytol as a labeling agent of human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) to facilitate tracking by magnetic resonance imaging (MRI) in a large animal model. Differentiating hESCs were exposed to ferumoxytol at different time points and varying concentrations. We determined that treatment with ferumoxytol at 300 mg/ml on day 0 of cardiac differentiation offered adequate cell viability and signal intensity for MRI detection without compromising further differentiation into definitive cardiac lineages. Labeled hESC-CPCs were transplanted by open surgical methods into the left ventricular free wall of uninjured pig hearts and imaged both ex vivo and in vivo. Comprehensive T 2 *-weighted images were obtained immediately after transplantation and 40 days later before termination. The localization and dispersion of labeled cells could be effectively imaged and tracked at days 0 and 40 by MRI. Thus, under the described conditions, ferumoxytol can be used as a long-term, differentiation-neutral cell-labeling agent to track transplanted hESC-CPCs in vivo using MRI. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:67-74 SIGNIFICANCEThe development of a safe and reproducible in vivo imaging technique to track the fate of transplanted human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) is a necessary step to clinical translation. An iron oxide nanoparticle (ferumoxytol)-based approach was used for cell labeling and subsequent in vivo magnetic resonance imaging monitoring of hESC-CPCs transplanted into uninjured pig hearts. The present results demonstrate the use of ferumoxytol labeling and imaging techniques in tracking the location and dispersion of cell grafts, highlighting its utility in future cardiac stem cell therapy trials.

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Ferumoxytol: A New, Clinically Applicable Label for Stem-Cell Tracking in Arthritic Joints with MRI

Cited by 79 publications

References 61 publications

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

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

Nanoparticles and clinically applicable cell tracking

Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

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