Efficient stem cell labeling for MRI studies

Küstermann, Ekkehard; Himmelreich, Uwe; Kandal, Korinna; Geelen, Tessa; Ketkar, Alhad Ashok; Wiedermann, Dirk; Strecker, Cordula; Esser, Johannes M.; Arnhold, Stefan; Hoehn, Mathias

doi:10.1002/cmmi.229

Cited by 78 publications

(101 citation statements)

References 37 publications

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“…Numerous studies have shown that in vitro neural stem and progenitor cells can be loaded with iron oxyde particles (for review CouillardDespres & Aigner 2011). It has been suggested that this method has a very low detection threshold (Kustermann et al 2008). One limitation of this method is that the detected contrast on MR images refers only to the particles and not to the labelled cells themselves.…”

Section: Inorganic Nanoparticlesmentioning

confidence: 99%

MRI Techniques and New Animal Models for Imaging the Brain

Chaillou¹,

Tillet²,

Andersson³

2012

When Things Go Wrong - Diseases and Disorders of the Human Brain

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Section: Inorganic Nanoparticlesmentioning

confidence: 99%

MRI Techniques and New Animal Models for Imaging the Brain

Chaillou¹,

Tillet²,

Andersson³

2012

When Things Go Wrong - Diseases and Disorders of the Human Brain

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“…This is mainly due to dilution of (U)SPIOs with cell division but might also occur due to exocytosis phantoms in vitro, can also be monitored by MRI following transplantation in vivo. When grafted in either of the particles (24). The PDT of mESC and rMAPC was 12 h, whereas the PDT for mMSC was 48 h, which mouse or rat brain, with or without stroke, labeled rMAPC were visualized until 15 days after transplantaexplains the significant reduction of iron in rMAPC.…”

Section: Phenotype and Genetic Integrity Effect Of Labeling On Stem mentioning

confidence: 99%

Effects of MRI Contrast Agents on the Stem Cell Phenotype

et al. 2010

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The ultimate therapy for ischemic stroke is restoration of blood supply in the ischemic region and regeneration of lost neural cells. This might be achieved by transplanting cells that differentiate into vascular or neuronal cell types, or secrete trophic factors that enhance self-renewal, recruitment, long-term survival, and functional integration of endogenous stem/progenitor cells. Experimental stroke models have been developed to determine potential beneficial effect of stem/progenitor cell-based therapies. To follow the fate of grafted cells in vivo, a number of noninvasive imaging approaches have been developed. Magnetic resonance imaging (MRI) is a high-resolution, clinically relevant method allowing in vivo monitoring of cells labeled with contrast agents. In this study, labeling efficiency of three different stem cell populations [mouse embryonic stem cells (mESC), rat multipotent adult progenitor cells (rMAPC), and mouse mesenchymal stem cells (mMSC)] with three different (ultra)small superparamagnetic iron oxide [(U)SPIO] particles (Resovist, Endorem, Sinerem) was compared. Labeling efficiency with Resovist and Endorem differed significantly between the different stem cells. Labeling with (U)SPIOs in the range that allows detection of cells by in vivo MRI did not affect differentiation of stem cells when labeled with concentrations of particles needed for MRI-based visualization. Finally, we demonstrated that labeled rMAPC could be detected in vivo and that labeling did not interfere with their migration. We conclude that successful use of (U)SPIOs for MRI-based visualization will require assessment of the optimal (U)SPIO for each individual (stem) cell population to ensure the most sensitive detection without associated toxicity.

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“…The majority of studies have used iron oxide-based nanoparticles (NPs) due to their relatively high sensitivity and their acceptable biocompatibility. 15,17,18,24,25,26 Several studies have evaluated potential toxic or adverse effects of intracellular iron oxide in cells, where the major focus has been the comparison of different NP-related properties (size, coating, and concentrations). 25,27 Furthermore, in studies where material-related properties have been the subject of scrutiny, cell-related properties have rarely been addressed.…”

Section: Introductionmentioning

confidence: 99%

Variability in contrast agent uptake by different but similar stem cell types

Ketkar-Atre

Struys

Soenen

et al. 2013

IJN

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The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI) contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP)-specific parameters. Here, we have studied three different types of NPs (Endorem®, magnetoliposomes [MLs], and citrate coated C-200) to label relatively larger, mesenchymal stem cells (MSCs) and, much smaller yet faster proliferating, multipotent adult progenitor cells (MAPCs). Both cell types are similar, as they are isolated from bone marrow and have substantial regenerative potential, which make them interesting candidates for comparative experiments. Using NPs with different surface coatings and sizes, we found that differences in the proliferative and morphological characteristics of the cells used in the study are mainly responsible for the fate of endocytosed iron, intracellular iron concentration, and cytotoxic responses. The quantitative analysis, using high-resolution electron microscopy images, demonstrated a strong relationship between cell volume/surface, uptake, and cytotoxicity. Interestingly, uptake and toxicity trends are reversed if intracellular concentrations, and not amounts, are considered. This indicates that more attention should be paid to cellular parameters such as cell size and proliferation rate in comparative cell-labeling studies.

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Efficient stem cell labeling for MRI studies

Cited by 78 publications

References 37 publications

MRI Techniques and New Animal Models for Imaging the Brain

MRI Techniques and New Animal Models for Imaging the Brain

Effects of MRI Contrast Agents on the Stem Cell Phenotype

Variability in contrast agent uptake by different but similar stem cell types

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