Labeling of human mesenchymal stromal cells with superparamagnetic iron oxide leads to a decrease in migration capacity and colony formation ability

Schäfer, Richard; Kehlbach, Rainer; Müller, Michaela; Bantleon, Rüdiger; Kluba, Torsten; Ayturan, Miriam; Siegel, Georg; Wolburg, Hartwig; Northoff, Hinnak; Dietz, Klaus; Claussen, Claus D.; Wiskirchen, Jakub

doi:10.1080/14653240802666043

Cited by 81 publications

(82 citation statements)

References 40 publications

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“…Due to this increased number of applications in biological systems, assessment of the sensitivity, toxicity, and adverse effects of NPs on cell biology has become a topic of interest. An extensive number of studies have evaluated the effect of NP labeling on cell homeostasis; some of which have pointed to negative effects of particle incorporation on cell viability, 38 actin cytoskeleton structure, 39 differentiation potential, 40,41 receptor expression, 42,43 migratory capabilities, 44,45 and reactive oxygen species (ROS) generation, 46 suggesting the need for in vitro evaluation before their in vivo application. The number of studies focusing on cell-related rather than NPrelated parameters is limited.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Due to the partially complicated labeling protocols, simplified strategies using clinically approved materials (e. g. Endorem ® /Feridex ® , Superfect ® , Lipofectamine Plus ® , poly-Llysine (PLL), protamine) and low cell toxicity have been described in recent years [148,149]. While most studies do not describe any significant changes in cell behavior (e. g. apoptosis rate, proliferation index, differentiation behavior) [150,151], individual studies show changes in migration behavior and the ability to form colonies [152], in cell vitality [153], in differentiation behavior [154], or in the expression pattern [152]. By the same token, the influence of cell labeling on the long-term behavior of cells and the course of disease is currently unclear [155] and must be studied more closely in the future [156].…”

Section: Cell Labeling and Cell Imaging In Mrimentioning

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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“…Basic characterization included the evaluation of the differentiation potential into 3 mesenchymal lineages at passage 2 and 4: specifically into the adipogenic, osteogenic, and chondrogenic lineages as described previously [20]. The differentiated MSCs were stained with Oil Red O for adipogenesis, alkaline phosphatase for osteogenesis, and with Alcian Blue for chondrogenesis.…”

Section: Isolation and Culture Of Bm-derived Hmscs And Mmscsmentioning

confidence: 99%

Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential

Siegel¹,

Krause²,

Wöhrle³

et al. 2012

Stem Cells and Development

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Despite their paracrine activites, cardiomyogenic differentiation of bone marrow (BM)-derived mesenchymal stem cells (MSCs) is thought to contribute to cardiac regeneration. To systematically evaluate the role of differentiation in MSC-mediated cardiac regeneration, the cardiomyogenic differentiation potential of human MSCs (hMSCs) and murine MSCs (mMSCs) was investigated in vitro and in vivo by inducing cardiomyogenic and noncardiomyogenic differentiation. Untreated hMSCs showed upregulation of cardiac tropopin I, cardiac actin, and myosin light chain mRNA and protein, and treatment of hMSCs with various cardiomyogenic differentiation media led to an enhanced expression of cardiomyogenic genes and proteins; however, no functional cardiomyogenic differentiation of hMSCs was observed. Moreover, co-culturing of hMSCs with cardiomyocytes derived from murine pluripotent cells (mcP19) or with murine fetal cardiomyocytes (mfCMCs) did not result in functional cardiomyogenic differentiation of hMSCs. Despite direct contact to beating mfCMCs, hMSCs could be effectively differentiated into cells of only the adipogenic and osteogenic lineage. After intramyocardial transplantation into a mouse model of myocardial infarction, Sca-1 + mMSCs migrated to the infarcted area and survived at least 14 days but showed inconsistent evidence of functional cardiomyogenic differentiation. Neither in vitro treatment nor intramyocardial transplantation of MSCs reliably generated MSC-derived cardiomyocytes, indicating that functional cardiomyogenic differentiation of BM-derived MSCs is a rare event and, therefore, may not be the main contributor to cardiac regeneration.

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Labeling of human mesenchymal stromal cells with superparamagnetic iron oxide leads to a decrease in migration capacity and colony formation ability

Cited by 81 publications

References 40 publications

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

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

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

Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential

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