Labeling Human Mesenchymal Stem Cells with Fluorescent Contrast Agents: the Biological Impact

Boddington, Sophie; Sutton, Elizabeth; Henning, Tobias D.; Nedopil, Alexander J.; Sennino, Barbara; Kim, Anne; Daldrup-Link, Heike E.

doi:10.1007/s11307-010-0322-0

Cited by 28 publications

(26 citation statements)

References 16 publications

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“…4A). Cell labeling with nanoparticles has been reported to inhibit chondrogenesis in hMSCs (20). Although the SiNP-loaded cells differentiated down the chondrocyte lineage, we noted a reduced staining intensity compared with unloaded controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

Intracellular Aggregation of Multimodal Silica Nanoparticles for Ultrasound-Guided Stem Cell Implantation

2013

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The promises of cardiac stem cell therapy have yet to be fully realized, in part because of poor survival and engraftment efficacy of implanted cells. Cells die after implantation owing to ischemia, inflammation, immune response, as well as mis-injection or implantation into fibrotic tissue. Imaging tools can help implant cells in areas of the heart most receptive to stem cell therapy and monitor the efficacy of treatment by reporting the viability, location, and number of implanted stem cells. We describe a multimodal, silica-based nanoparticle that can be used for cell sorting (fluorescence), real-time guided cell implantation ultrasound, and high-resolution, long-term monitoring by magnetic resonance imaging (MRI). The nanoparticle agent increased the ultrasound and MRI contrast of labeled human mesenchymal stem cells (hMSCs) 700 and 200% versus unlabeled cells, respectively, and allowed cell imaging in animal models for 13 days after implantation. The agent had no significant impact on hMSC cell metabolic activity, proliferation, or pluripotency, and it increased the production of many paracrine factors implicated in cardiac repair. Electron microscopy and ultrasound imaging suggest that the mechanism of action is in vivo aggregation of the 300-nm silica nanoparticles into larger silica frameworks that amplify the ultrasound backscatter. The detection limit in cardiac tissue was 250,000 hMSCs via MRI and 70,000 via ultrasound. This ultrasound-guided cell delivery and multimodal optical/ultrasound/MRI intra-cardiac cell-tracking platform could improve cell therapy in the clinic by minimizing misdelivery or implantation into fibrotic tissue.

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Section: Resultsmentioning

confidence: 99%

Intracellular Aggregation of Multimodal Silica Nanoparticles for Ultrasound-Guided Stem Cell Implantation

2013

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“…However, the toxic potential of cadmium nanoparticles has remained a concern [20]. Boddington et al reported [21] that the iron oxide nanoparticle ferucarbotran may impair MSC differentiation, which hinders their potential use as fluorescence tracers for stem cells. In contrast, the toxicological effects of amorphous silica have been characterized reasonably well, and this form has been found to be less toxic in animal experiments than that of other nanomaterials.…”

Section: Discussionmentioning

confidence: 99%

Canine mesenchymal stem cells are effectively labeled with silica nanoparticles and unambiguously visualized in highly autofluorescent tissues

et al. 2012

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BackgroundDevelopment of a method for long-term labeling of cells is critical to elucidate transplanted cell fate and migration as well as the contribution to tissue regeneration. Silica nanoparticles have been recently developed and demonstrated to be biocompatible with a high labeling capacity. Thus, our study was designed to assess the suitability of silica nanoparticles for labeling canine mesenchymal stem cells (MSCs) and the fluorescence afficiency in highly autofluorescent tissue.ResultsWe examined the effect of silica nanoparticle labeling on stem cell morphology, viability and differentiation as compared with those of unlabeled control cells. After 4 h of incubation with silica nanoparticles, they were internalized by canine MSCs without a change in the morphology of cells compared with that of control cells. The viability and proliferation of MSCs labeled with silica nanoparticles were evaluated by a WST-1 assay and trypan blue exclusion. No effects on cell viability were observed, and the proliferation of canine MSCs was not inhibited during culture with silica nanoparticles. Furthermore, adipogenic and osteogenic differentiation of silica nanoparticle-labeled canine MSCs was at a similar level compared with that of unlabeled cells, indicating that silica nanoparticle labeling did not alter the differentiation capacity of canine MSCs. Silica nanoparticle-labeled canine MSCs were injected into the kidneys of BALB/c mice after celiotomy, and then the mice were sacrificed after 2 or 3 weeks. The localization of injected MSCs was closely examined in highly autofluorescent renal tissues. Histologically, canine MSCs were uniformly and completely labeled with silica nanoparticles, and were unambiguously imaged in histological sections.ConclusionsThe results of the current study showed that silica nanoparticles are useful as an effective labeling marker for MSCs, which can elucidate the distribution and fate of transplanted MSCs.

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“…A major challenge in the treatment of cartilage defects due to arthritis is the lack of self-regeneration capacity of the injured cartilage [3, 4] . New therapies based on matrix-associated chondrocyte implants or matrix-associated stem-cell transplants (MASIs) provide a potentially curative therapeutic option [5–10] .…”

mentioning

confidence: 99%

“…MRI is currently the only noninvasive diagnostic test that can provide high-resolution anatomical and functional information of cartilage defects in vivo [5,13–16]. A variety of iron oxide nanoparticle-based stem-cell markers have been previously applied for cell-tracking purposes [15, 17–21] .…”

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confidence: 99%

Ferumoxytol: A New, Clinically Applicable Label for Stem-Cell Tracking in Arthritic Joints with MRI

et al. 2013

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Aim To develop a clinically applicable MRI technique for tracking stem cells in matrix-associated stem-cell implants, using the US FDA-approved iron supplement ferumoxytol. Materials & methods Ferumoxytol-labeling of adipose-derived stem cells (ADSCs) was optimized in vitro. A total of 11 rats with osteochondral defects of both femurs were implanted with ferumoxytol- or ferumoxides-labeled or unlabeled ADSCs, and underwent MRI up to 4 weeks post matrix-associated stem-cell implant. The signal-to-noise ratio of different matrix-associated stem-cell implant was compared with t-tests and correlated with histopathology. Results An incubation concentration of 500 µg iron/ml ferumoxytol and 10 µg/ml protamine sulfate led to significant cellular iron uptake, T2 signal effects and unimpaired ADSC viability. In vivo, ferumoxytol-and ferumoxides-labeled ADSCs demonstrated significantly lower signal-to-noise ratio values compared with unlabeled controls (p < 0.01). Histopathology confirmed engraftment of labeled ADSCs, with slow dilution of the iron label over time. Conclusion Ferumoxytol can be used for in vivo tracking of stem cells with MRI.

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Labeling Human Mesenchymal Stem Cells with Fluorescent Contrast Agents: the Biological Impact

Cited by 28 publications

References 16 publications

Intracellular Aggregation of Multimodal Silica Nanoparticles for Ultrasound-Guided Stem Cell Implantation

Intracellular Aggregation of Multimodal Silica Nanoparticles for Ultrasound-Guided Stem Cell Implantation

Canine mesenchymal stem cells are effectively labeled with silica nanoparticles and unambiguously visualized in highly autofluorescent tissues

Ferumoxytol: A New, Clinically Applicable Label for Stem-Cell Tracking in Arthritic Joints with MRI

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