Non-invasive tracking of human haemopoietic CD34+ stem cells in vivo in immunodeficient mice by using magnetic resonance imaging

Niemeyer, Markus; Oostendorp, Robert A.J.; Kremer, Markus; Hippauf, Sandra; Jacobs, Volker R.; Baurecht, Hansjörg; Ludwig, Georg; Piontek, Guido; Bekker-Ruz, Viktoria; Timmer, Sebastian; Rummeny, Ernst J.; Kiechle, Marion; Beer, Ambros J.

doi:10.1007/s00330-010-1773-z

Cited by 22 publications

(47 citation statements)

References 26 publications

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“…We used a multidisciplinary approach based on magnetic resonance imaging (MRI), flow cytometry, and immunohistology to monitor the fate of hematopoietic stem and progenitor cells (HSPCs), retrieved by lineage negative (Lin − ) selection from the murine bone marrow (BM), upon transplantation into naïve congenic recipients. Superparamagnetic iron oxide (SPIO) particles were used for rendering HSPCs detectable by MRI in short-term studies (14,15), whereas GFP-encoding lentiviral vectors (LVs) were used to track genetically marked cells long-term (Fig. S1).…”

Section: Resultsmentioning

confidence: 99%

Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation

Capotondo

Milazzo

Politi³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

184

187

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The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs), for which hematopoietic cell transplantation (HCT) is applied to repopulate the recipient myeloid compartment, including microglia, with cells expressing the defective functional hydrolase. By studying wild-type and LSD mice at diverse time-points after HCT, we showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. However, only the use of a conditioning regimen capable of ablating functionally defined brain-resident myeloid precursors allowed turnover of microglia with the donor, mediated by local proliferation of early immigrants rather than entrance of mature cells from the circulation.

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Section: Resultsmentioning

confidence: 99%

Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation

Capotondo

Milazzo

Politi³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

184

187

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“…In these cases, the use of lower field strength MRI significantly limited the spatial resolution of the transplanted cells, and in effect determined BM cell homing by the loss of signal of entire target organs. 17,29,30 In addition, one of these experiments circumvented the process of homing by injecting the labeled cells directly into the marrow cavity. 29 The collective results of these studies showed the potential for MRI to study BM engraftment, but highlighted the need to significantly increase sensitivity and resolution to utilize negative contrast agents such as Feridex.…”

Section: Discussionmentioning

confidence: 99%

Ultra-high-field MRI real-time imaging of HSC engraftment of the bone marrow niche

et al. 2011

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The bone marrow (BM) undergoes extensive remodeling following irradiation damage. A crucial part of restoring homeostasis following irradiation is the ability of hematopoietic stem cells (HSCs) to home to and engraft specialized niches within the BM through a remodeling BM vascular system. Here we show that a combination of ultra-high-field strength magnetic resonance imaging (17.6 T, MRI) coupled with fluorescent microscopy (FLM) serves as a powerful tool for the in vivo imaging of cell homing within the BM. Ultra-high-field MRI can achieve high-resolution three-dimensional (3D) images (28 Â 28 Â 60 lm 3 ) of the BM in live mice, sufficient to resolve anatomical changes in BM microstructures attributed to radiation damage. Following intra-arterial infusion with dsRedexpressing BM cells, labeled with superparamagnetic iron oxides, both FLM and MRI could be used to follow initial homing and engraftment of donor HSC to a limited number of preferred sites within a few cell diameters of the calcified boneFthe endosteal niche. Subsequent histology confirmed the fidelity and accuracy of MRI to create non-invasive, highresolution 3D images of donor cell engraftment of the BM in living animals at the level of single-cell detection.

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“…[22][23][24][25][26] Assessing the possible negative effects of SPIO labeling on the stem cell phenotype and cell behavior, reports significantly differ and range from no effect to a minimal negative effect on cell viability to inhibition of differentiation and migration. [23][24][25][27][28][29][30] As not only labeling efficiency, but also cell survival and behavior appears cell and SPIO dependent, proliferation and differentiation analysis should be considered when labeling stem cells with SPIO.…”

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confidence: 99%

Viability, Differentiation Capacity, and Detectability of Super-Paramagnetic Iron Oxide-Labeled Muscle Precursor Cells for Magnetic-Resonance Imaging

Azzabi

Rottmar

Jovaisaite

et al. 2015

Tissue Engineering Part C: Methods

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Cell therapies are a promising approach for the treatment of a variety of human conditions including stress urinary incontinence, but their success greatly depends on the biodistribution, migration, survival, and differentiation of the transplanted cells. Noninvasive in vivo cell tracking therefore presents an important aspect for translation of such a procedure into the clinics. Upon labeling with superparamagnetic iron oxide (SPIO) nanoparticles, cells can be tracked by magnetic resonance imaging (MRI), but possible adverse effect of the labeling have to be considered when labeling stem cells with SPIOs. In this study, human muscle precursor cells (hMPC) were labeled with increasing concentrations of SPIO nanoparticles (100-1600 mg/mL) and cell viability and differentiation capacity upon labeling was assessed in vitro. While a linear dependence between cell viability and nanoparticle concentration could be observed, differentiation capacity was not affected by the presence of SPIOs. Using a nude mouse model, a concentration (400 mg/mL) could be defined that allows reliable detection of hMPCs by MRI but does not influence myogenic in vivo differentiation to mature and functional muscle tissue. This suggests that such an approach can be safely used in a clinical setting to track muscle regeneration in patients undergoing cell therapy without negative effects on the functionality of the bioengineered muscle.

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Non-invasive tracking of human haemopoietic CD34+ stem cells in vivo in immunodeficient mice by using magnetic resonance imaging

Abstract: Intravenously administered Resovist-labelled CD34(+) cells home to bone marrow of mice. Homing can be tracked in vivo by using clinical 1.5-T MR imaging technology.

Cited by 22 publications

References 26 publications

Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation

Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation

Ultra-high-field MRI real-time imaging of HSC engraftment of the bone marrow niche

Viability, Differentiation Capacity, and Detectability of Super-Paramagnetic Iron Oxide-Labeled Muscle Precursor Cells for Magnetic-Resonance Imaging

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