<sup>18</sup>F-FDG Labeling of Mesenchymal Stem Cells and Multipotent Adult Progenitor Cells for PET Imaging: Effects on Ultrastructure and Differentiation Capacity

Wolfs, Esther; Struys, Tom; Notelaers, Tineke; Roberts, Simon C.; Sohni, Abhishek; Bormans, Guy; Laere, Koen Van; Luyten, Frank P.; Gheysens, Olivier; Lambrichts, Ivo; Verfaillie, Catherine M.; Deroose, Christophe M.

doi:10.2967/jnumed.112.108316

Cited by 64 publications

(57 citation statements)

References 36 publications

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“…Furthermore, macrophages can engulf dead MSCs containing nanoparticles, which will interfere with the tracking of labeled stem cells [12][13][14]. The in vivo application of 18FDG labeling has been limited to early biodistribution studies and requires positron emission tomography [7]. Therefore, BrdU, magnetic nanoparticles and 18FDG are not ideal biomarkers for studying hPMSCs.…”

Section: Discussionmentioning

confidence: 99%

GFP Labeling and Hepatic Differentiation Potential of Human Placenta-Derived Mesenchymal Stem Cells

Su²,

Zhu³

et al. 2015

Cell Physiol Biochem

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Background: Stem cell-based therapy in liver diseases has received increasing interest over the past decade, but direct evidence of the homing and implantation of transplanted cells is conflicting. Reliable labeling and tracking techniques are essential but lacking. The purpose of this study was to establish human placenta-derived mesenchymal stem cells (hPMSCs) expressing green fluorescent protein (GFP) and to assay their hepatic functional differentiation in vitro. Methods: The GFP gene was transduced into hPMSCs using a lentivirus to establish GFP⁺ hPMSCs. GFP⁺ hPMSCs were analyzed for their phenotypic profile, viability and adipogenic, osteogenic and hepatic differentiation. The derived GFP⁺ hepatocyte-like cells were evaluated for their metabolic, synthetic and secretory functions, respectively. Results: GFP⁺ hPMSCs expressed high levels of HLA I, CD13, CD105, CD73, CD90, CD44 and CD29, but were negative for HLA II, CD45, CD31, CD34, CD133, CD271 and CD79. They possessed adipogenic, osteogenic and hepatic differentiation potential. Hepatocyte-like cells derived from GFP⁺ hPMSCs showed typical hepatic phenotypes. Conclusions: GFP gene transduction has no adverse influences on the cellular or biochemical properties of hPMSCs or markers. GFP gene transduction using lentiviral vectors is a reliable labeling and tracking method. GFP⁺ hPMSCs can therefore serve as a tool to investigate the mechanisms of MSC-based therapy, including hepatic disease therapy.

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Section: Discussionmentioning

confidence: 99%

GFP Labeling and Hepatic Differentiation Potential of Human Placenta-Derived Mesenchymal Stem Cells

Su²,

Zhu³

et al. 2015

Cell Physiol Biochem

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“…When compared with SPECT, PET is at least 10 times more sensitive, potentiating reduction of radioexposure of the cells by one log (26). Fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) has been used to label cells ex vivo, however, the half-life of 18 F is short (109.7 minutes); moreover, dormant or inactivated cells with low glucose metabolism take up insufficient 18 F FDG, and the cells can release 18 F FDG via phosphatase activity (27,28).…”

Section: Fundingmentioning

confidence: 99%

⁸⁹Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies

Sato¹,

Wu²,

Asiedu³

et al. 2015

Radiology

131

177

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Purpose:To develop a clinically translatable method of cell labeling with zirconium 89 ( 89 Zr) and oxine to track cells with positron emission tomography (PET) in mouse models of cell-based therapy. Materials andMethods:This study was approved by the institutional animal care committee. 89Zr-oxine complex was synthesized in an aqueous solution. Cell labeling conditions were optimized by using EL4 mouse lymphoma cells, and labeling efficiency was examined by using dendritic cells (DCs) (n = 4), naïve (n = 3) and activated (n = 3) cytotoxic T cells (CTLs), and natural killer (NK) (n = 4), bone marrow (n = 4), and EL4 (n = 4) cells. The effect of ] cells, n = 4) and by measuring the tumor size (n = 6). Two-way analysis of variance was used to compare labeling conditions, the Wilcoxon test was used to assess cell survival and proliferation, and Holm-Sidak multiple tests were used to assess tumor growth and perform biodistribution analyses. Results:89 Zr-oxine complex was synthesized at a mean yield of 97.3% 6 2.8 (standard deviation). It readily labeled cells at room temperature or 4°C in phosphate-buffered saline (labeling efficiency range, 13.0%-43.9%) and was stably retained (83.5% 6 1.8 retention on day 5 in DCs). Labeling did not affect the viability of DCs and CTLs when compared with nonlabeled control mice (P . .05), nor did it affect functionality. 89Zr-oxine complex enabled extended cell tracking for 7 days. Labeled tumor-specific CTLs accumulated in the tumor (4.6% on day 7) and induced tumor regression (P , .05 on day 7). Conclusion:We have developed a 89Zr-oxine complex cell tracking technique for use with PET that is applicable to a broad range of cell types and could be a valuable tool with which to evaluate various cell-based therapies.q RSNA, 2015

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“…65,66 [ 18 F]-2-fluoro-2-deoxy-glucose ( 18 F-FDG) is the most common PET probe, and has been investigated to monitor the distributions of various stem cells after injection in small animal models. Wolfs et al 67 evaluated the effects of 18 F-FDG-labeling on the cellular functions and ultrastructures of mouse MSCs and rat adult progenitor cells. They noted that proliferations of both cells and their ultrastructures, such as mitochondrial length, lysosome size, the number of lysosomes, the number of vacuoles, and the average rough endoplasmic reticulum width, were not influenced by the labeling procedure.…”

Section: Current Stem Cell Imaging Technologiesmentioning

confidence: 99%

Molecular imaging for In vivo tracking of stem cell fate

et al. 2014

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Stem cells have a potential to dramatically change the common modalities of treatment for many diseases. Despite their rapid transition from animal studies to clinical applications, a number of unanswered questions remain regarding in vivo behaviors of stem cells transplanted into target tissues, including questions about their survival, distribution, migration, differentiation, and tumorigenicity. Recent advances in noninvasive molecular imaging technologies, including optical imaging, magnetic resonance imaging (MRI), radionuclide imaging, and reporter genebased imaging, have gradually elucidated the fundamental behaviors of stem cells via in vivo real time qualitative and quantitative monitoring. Here, we briefly review current imaging techniques for tracking stem cells, with an emphasis on the advantages and drawbacks of each imaging approach, and discuss future prospects for in vivo tracking of stem cells in regenerative medicine.

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¹⁸F-FDG Labeling of Mesenchymal Stem Cells and Multipotent Adult Progenitor Cells for PET Imaging: Effects on Ultrastructure and Differentiation Capacity

Cited by 64 publications

References 36 publications

GFP Labeling and Hepatic Differentiation Potential of Human Placenta-Derived Mesenchymal Stem Cells

GFP Labeling and Hepatic Differentiation Potential of Human Placenta-Derived Mesenchymal Stem Cells

⁸⁹Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies

Molecular imaging for In vivo tracking of stem cell fate

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18F-FDG Labeling of Mesenchymal Stem Cells and Multipotent Adult Progenitor Cells for PET Imaging: Effects on Ultrastructure and Differentiation Capacity

Cited by 64 publications

References 36 publications

GFP Labeling and Hepatic Differentiation Potential of Human Placenta-Derived Mesenchymal Stem Cells

GFP Labeling and Hepatic Differentiation Potential of Human Placenta-Derived Mesenchymal Stem Cells

89Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies

Molecular imaging for In vivo tracking of stem cell fate

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Product

Resources

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¹⁸F-FDG Labeling of Mesenchymal Stem Cells and Multipotent Adult Progenitor Cells for PET Imaging: Effects on Ultrastructure and Differentiation Capacity

⁸⁹Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies