Superparamagnetic iron oxide does not affect the viability and function of adipose-derived stem cells, and superparamagnetic iron oxide–enhanced magnetic resonance imaging identifies viable cells

Wang, Lei; Deng, Jixian; Wang, Jian; Xiang, Bo; Yang, Tonghua; Gruwel, Marco L.H.; Kashour, Tarek; Tomanek, Bogusław; Summer, Randy; Freed, Darren H.; Jassal, Davinder S.; Dai, Guangping; Glogowski, Miriam; Deslauriers, Roxanne; Arora, Rakesh C.; Tian, Ganghong

doi:10.1016/j.mri.2008.05.013

Cited by 44 publications

(36 citation statements)

References 29 publications

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“…16 We have demonstrated in vitro that viability, cytokine production, and migratory capacity are unaffected by SPIO labeling. This is consistent with the majority of studies that have shown preservation of both viability and function after SPIO labeling of a variety of cell types including mesenchymal, hematopoietic, neural, and adipose-derived stem cells, [6][7][8][9][10][11] with only a few reporting adverse effects and 1 showing increased proliferation of SPIO-labeled mesenchymal stem cells. [17][18][19] It is worth recognizing the diversity in cell-labeling protocols used across these studies that may explain such findings.…”

Section: Discussionsupporting

confidence: 89%

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In Vivo Mononuclear Cell Tracking Using Superparamagnetic Particles of Iron Oxide

Richards

Shaw

Lang

et al. 2012

Circ: Cardiovascular Imaging

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Background-Cell therapy is an emerging and exciting novel treatment option for cardiovascular disease that relies on the delivery of functional cells to their target site. Monitoring and tracking cells to ensure tissue delivery and engraftment is a critical step in establishing clinical and therapeutic efficacy. The study aims were (1) to develop a Good Manufacturing Practice-compliant method of labeling competent peripheral blood mononuclear cells with superparamagnetic particles of iron oxide (SPIO), and (2) to evaluate its potential for magnetic resonance cell tracking in humans. Methods and Results-Peripheral blood mononuclear cells 1-5×10 9 were labeled with SPIO. SPIO-labeled cells had similar in vitro viability, migratory capacity, and pattern of cytokine release to unlabeled cells. After intramuscular administration, up to 10 8 SPIO-labeled cells were readily identifiable in vivo for at least 7 days using magnetic resonance imaging scanning. Using a phased-dosing study, we demonstrated that systemic delivery of up to 10 9 SPIO-labeled cells in humans is safe, and cells accumulating in the reticuloendothelial system were detectable on clinical magnetic resonance imaging. In a healthy volunteer model, a focus of cutaneous inflammation was induced in the thigh by intradermal injection of tuberculin. Intravenously delivered SPIO-labeled cells tracked to the inflamed skin and were detectable on magnetic resonance imaging. Prussian blue staining of skin biopsies confirmed iron-laden cells in the inflamed skin. Conclusions-Human

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Section: Discussionsupporting

confidence: 89%

“…SPIO are not toxic to cells and are biodegradable in vivo. [6][7][8][9][10][11] It is important to note, however, that the safety of intravenous administration of SPIO-labeled cells in humans has yet to be demonstrated, and would be critical for the development and Food and Drug Administration approval of novel clinical cell-tracking agents.…”

mentioning

confidence: 99%

In Vivo Mononuclear Cell Tracking Using Superparamagnetic Particles of Iron Oxide

Richards

Shaw

Lang

et al. 2012

Circ: Cardiovascular Imaging

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“…ASCs were prepared according to the method developed by Zuk et al [15] with modifications as previously described [16]. In brief, subcutaneous adipose tissue (3-4 g) was obtained from the abdominal and inguinal regions of inbred male Lewis rats.…”

Section: Preparation Of Ascsmentioning

confidence: 99%

“…Expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and insulin-like growth factor (IGF-I) by ASCs were assessed with RT-PCR to determine effects of the radioactivity on function of the stem cells. Adipogenic and osteogenic differentiation of ASCs were also evaluated histochemically using methods described previously [16]. Adipogenic differentiation was also evaluated by staining the cells with oil red O stain, which stains intracellular lipid deposits red.…”

Section: Induction Of Differentiation In Ascsmentioning

confidence: 99%

Viability and proliferation potential of adipose-derived stem cells following labeling with a positron-emitting radiotracer

Elhami

Goertzen

Xiang

et al. 2011

Eur J Nucl Med Mol Imaging

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Purpose Adipose-derived stem cells (ASCs) have promising potential in regenerative medicine and cell therapy. Our objective is to examine the biological function of the labeled stem cells following labeling with a readily available positron emission tomography (PET) tracer, 18 F-fluoro-2-deoxy-D-glucose (FDG). In this work we characterize labeling efficiency through assessment of FDG uptake and retention by the ASCs and the effect of FDG on cell viability, proliferation, transdifferentiation, and cell function in vitro using rat ASCs. Methods Samples of 105 ASCs (from visceral fat tissue) were labeled with concentrations of FDG (1-55 Bq/cell) in 0.75 ml culture medium. Label uptake and retention, as a function of labeling time, FDG concentration, and efflux period were measured to determine optimum cell labeling conditions. Cell viability, proliferation, DNA structure damage, cell differentiation, and other cell functions were examined. Non-labeled ASC samples were used as a control for all experimental groups. Labeled ASCs were injected via tail vein in several healthy rats and initial cell biodistribution was assessed.Results Our results showed that FDG uptake and retention by the stem cells did not depend on FDG concentration but on labeling and efflux periods and glucose content of the labeling and efflux media. Cell viability, transdifferentiation, and cell function were not greatly affected. DNA damage due to FDG radioactivity was acute, but reversible; cells managed to repair the damage and continue with cell cycles. Over all, FDG (up to 25 Bq/cell) did not impose severe cytotoxicity in rat ASCs. Initial biodistribution of the FDG-labeled ASCs was 80% + retention in the lungs. In the delayed whole-body images (2-3 h postinjection) there was some activity distribution resembling typical FDG uptake patterns.Conclusion For in vivo cell tracking studies with PET tracers, the parameter of interest is the amount of radiotracer that is present in the cells being labeled and consequent biological effects. From our study we developed a labeling protocol for labeling ASCs with a readily available PET tracer, FDG. Our results indicate that ASCs can be safely labeled with FDG concentration up to 25 Bq/cell, without compromising their biological function. A labeling period of 90 min in glucose-free medium and efflux of 60 min in complete media resulted in optimum label retention, i.e., 60% + by the stem cells. The initial biodistribution of the implanted FDG-labeled stem cells can be monitored using microPET imaging.

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“…SPIO cause inhomogeneity of magnetic field and SPIO-labeled cells appear as dark signal on T2*-and T2-weighted images. There have been many studies on the labeling of stem cells with SPIO particle [7][8][9][10][11][12][13][14][15][16][17][18]. However, stem cells lack phagocytic capacity and the amount of internalized SPIO may be insufficient for cellular imaging.…”

Section: Introductionmentioning

confidence: 99%

Tracking of transplanted mesenchymal stem cells labeled with fluorescent magnetic nanoparticle in liver cirrhosis rat model with 3-T MRI

Kim

Shim

et al. 2010

Magnetic Resonance Imaging

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Superparamagnetic iron oxide does not affect the viability and function of adipose-derived stem cells, and superparamagnetic iron oxide–enhanced magnetic resonance imaging identifies viable cells

Cited by 44 publications

References 29 publications

In Vivo Mononuclear Cell Tracking Using Superparamagnetic Particles of Iron Oxide

In Vivo Mononuclear Cell Tracking Using Superparamagnetic Particles of Iron Oxide

Viability and proliferation potential of adipose-derived stem cells following labeling with a positron-emitting radiotracer

Tracking of transplanted mesenchymal stem cells labeled with fluorescent magnetic nanoparticle in liver cirrhosis rat model with 3-T MRI

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