Long-Term Tracking Mesenchymal Stem Cell Differentiation with Photostable Fluorescent Nanoparticles

Background Nanoparticles show promise within the field of cancer therapeutics. Among the nanoparticle constructs, gold nanostars (GNSs) are unique nanoplatforms that can be imaged in real-time and transform light energy into heat to ablate cells. However, targeted delivery of GNSs to tumors remains a challenge. Adipose-derived stem cells (ASCs) migrate towards tumor niches in response to chemokines. The ability of ASCs to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics. Methods To test the labeling efficiency of GNSs, undifferentiated ASCs were incubated with GNSs and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence (TPL) microscopy. The effects of GNSs on cell phenotype, proliferation, and viability was assessed with flow cytometry, MTT metabolic assay, and trypan blue respectively. Tri-lineage differentiation of GNS-ASCs was induced with the appropriate media. For cellular ablation, photothermolysis was performed on ASCs cultured alone or in co-culture with SKBR3 cancer cells. Results Efficient uptake of GNSs occurred in ASCs, with persistence of the luminescent signal over 4-days. Labeling efficiency and signal quality was greater than Qtracker. GNSs did not affect cell phenotype, viability, or proliferation, and exhibited stronger luminescence than Qtracker throughout differentiation. Zones of complete ablation surrounding the GNS-ASCs were observed following photothermolysis in both monoculture and co-culture models. Conclusions These studies show that GNSs effectively label ASCs without altering cell phenotype. Once labeled, photoactivation of GNS-ASCs ablates neighboring cancer cells, demonstrating the potential of ASCs as a vehicle for the delivery of site-specific cancer therapy.

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“…This allows for superior nanotherapeutic capabilities in comparison to other commonly used nanoparticles (23, 51-54) .…”

Section: Discussionmentioning

confidence: 99%

Human Adipose-Derived Stem Cells Labeled with Plasmonic Gold Nanostars for Cellular Tracking and Photothermal Cancer Cell Ablation

Shammas

Fales

Crawford

et al. 2017

Plastic &Amp; Reconstructive Surgery

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“…16 The higher photon-to-heat conversion efficiency of GNS, which can be tuned to have spectral absorption in the near-infrared region where tissue absorbs least, makes GNS superior in biological imaging and nanotherapeutic capabilities as compared to other commonly used nanoparticles. 14,15,[17][18][19] With regard to in vivo translation, GNS can easily penetrate tumor vasculature via EPR effect that originates from the inherently leaky tumor vasculature. 20,21 Furthermore, once delivered to the tumor microenvironment, there is minimal clearance of nanoparticles that range from 10 to 100 nm in size due to lack of an efficient lymphatic system.…”

Section: Crawford Et Almentioning

confidence: 99%

Photothermal ablation of inflammatory breast cancer tumor emboli using plasmonic gold nanostars

Crawford¹,

Shammas²,

Fales³

et al. 2017

IJN

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Inflammatory breast cancer (IBC) is rare, but it is the most aggressive subtype of breast cancer. IBC has a unique presentation of diffuse tumor cell clusters called tumor emboli in the dermis of the chest wall that block lymph vessels causing a painful, erythematous, and edematous breast. Lack of effective therapeutic treatments has caused mortality rates of this cancer to reach 20%–30% in case of women with stage III–IV disease. Plasmonic nanoparticles, via photothermal ablation, are emerging as lead candidates in next-generation cancer treatment for site-specific cell death. Plasmonic gold nanostars (GNS) have an extremely large two-photon luminescence cross-section that allows real-time imaging through multiphoton microscopy, as well as superior photothermal conversion efficiency with highly concentrated heating due to its tip-enhanced plasmonic effect. To effectively study the use of GNS as a clinically plausible treatment of IBC, accurate three-dimensional (3D) preclinical models are needed. Here, we demonstrate a unique in vitro preclinical model that mimics the tumor emboli structures assumed by IBC in vivo using IBC cell lines SUM149 and SUM190. Furthermore, we demonstrate that GNS are endocytosed into multiple cancer cell lines irrespective of receptor status or drug resistance and that these nanoparticles penetrate the tumor embolic core in 3D culture, allowing effective photothermal ablation of the IBC tumor emboli. These results not only provide an avenue for optimizing the diagnostic and therapeutic application of GNS in the treatment of IBC but also support the continuous development of 3D in vitro models for investigating the efficacy of photothermal therapy as well as to further evaluate photothermal therapy in an IBC in vivo model.

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“…MRI techniques require the use of cells labeled with contrast agents that are photostable, non-toxic, biocompatible, and do not alter cell properties. 17 Iron oxide superparamagnetic nanoparticle formulations are considered as simple and effective contrast agents for MRI applications. 18 Such formulations exhibit strong negative contrast properties in both T 2 and T 2 *weighted MRI images, 19 and allow the histochemical detection of labeled cells by simple staining techniques.…”

Section: Introductionmentioning

confidence: 99%

<p>Efficient Labeling Of Mesenchymal Stem Cells For High Sensitivity Long-Term MRI Monitoring In Live Mice Brains</p>

Ali¹,

Shahror²,

Chen³

2020

IJN

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Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/R_ECxLGJvxw Background: Regenerative medicine field is still lagging due to the lack of adequate knowledge regarding the homing of therapeutic cells towards disease sites, tracking of cells during treatment, and monitoring the biodistribution and fate of cells. Such necessities require labeling of cells with imaging agents that do not alter their biological characteristics, and development of suitable non-invasive imaging modalities. Purpose: We aimed to develop, characterize, and standardize a facile labeling strategy for engineered mesenchymal stem cells without altering their viability, secretion of FGF21 protein (neuroprotective), and differentiation capabilities for non-invasive longitudinal MRI monitoring in live mice brains with high sensitivity. Methods: We compared the labeling efficiency of different commercial iron oxide nanoparticles towards our stem cells and determined the optimum labeling conditions using prussian blue staining, confocal microscopy, transmission electron microscopy, and flow cytometry. To investigate any change in biological characteristics of labeled cells, we tested their viability by WST-1 assay, expression of FGF21 by Western blot, and adipogenic and osteogenic differentiation capabilities. MRI contrast-enhancing properties of labeled cells were investigated in vitro using cell-agarose phantoms and in mice brains transplanted with the therapeutic stem cells. Results: We determined the nanoparticles that showed best labeling efficiency and least extracellular aggregation. We further optimized their labeling conditions (nanoparticles concentration and media supplementation) to achieve high cellular uptake and minimal extracellular aggregation of nanoparticles. Cell viability, expression of FGF21 protein, and differentiation capabilities were not impeded by nanoparticles labeling. Low number of labeled cells produced strong MRI signal decay in phantoms and in live mice brains which were visible for 4 weeks post transplantation. Conclusion: We established a standardized magnetic nanoparticle labeling platform for stem cells that were monitored longitudinally with high sensitivity in mice brains using MRI for regenerative medicine applications.

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Long-Term Tracking Mesenchymal Stem Cell Differentiation with Photostable Fluorescent Nanoparticles

Cited by 31 publications

References 30 publications

Human Adipose-Derived Stem Cells Labeled with Plasmonic Gold Nanostars for Cellular Tracking and Photothermal Cancer Cell Ablation

Human Adipose-Derived Stem Cells Labeled with Plasmonic Gold Nanostars for Cellular Tracking and Photothermal Cancer Cell Ablation

Photothermal ablation of inflammatory breast cancer tumor emboli using plasmonic gold nanostars

<p>Efficient Labeling Of Mesenchymal Stem Cells For High Sensitivity Long-Term MRI Monitoring In Live Mice Brains</p>

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