Design principles for noninvasive, longitudinal and quantitative cell tracking with nanoparticle-based CT imaging

Meir, Rinat; Betzer, Oshra; Motiei, Menachem; Kronfeld, Noam; Brodie, Chaya; Popovtzer, Rachela

doi:10.1016/j.nano.2016.09.013

Cited by 56 publications

(46 citation statements)

References 40 publications

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“…While micro-computed tomography (CT) imaging has good temporal resolution, it also has limited sensitivity and poor soft tissue contrast, which hampers its broad use in stem cell tracking applications. 10–12 Optical imaging also has good temporal resolution but is difficult to use clinically due to optical scatter that limits penetration depth. 13 …”

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confidence: 99%

Photoacoustic Imaging of Human Mesenchymal Stem Cells Labeled with Prussian Blue–Poly(l-lysine) Nanocomplexes

et al. 2017

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Acoustic imaging is affordable and accessible without ionizing radiation. Photoacoustic imaging increases the contrast of traditional ultrasound and can offer good spatial resolution when used at high frequencies with excellent temporal resolution. Prussian blue nanoparticles (PBNPs) are an emerging photoacoustic contrast agent with strong optical absorption in the near-infrared region. In this study, we developed a simple and efficient method to label human mesenchymal stem cells (hMSCs) with PBNPs and imaged them with photoacoustic imaging. First, PBNPs were synthesized by the reaction of FeCl3 with K4[Fe(CN)6] in the presence of citric acid and complexed with the cationic transfection agent poly-l-lysine (PLL). The PLL-coated PBNPs (PB-PLL nanocomplexes) have a maximum absorption peak at 715 nm and could efficiently label hMSCs. Cellular uptake of these nanocomplexes was studied using bright field, fluorescence, and transmission electron microscopy. The labeled stem cells were successfully differentiated into two downstream lineages of adipocytes and osteocytes, and they showed positive expression for surface markers of CD73, CD90, and CD105. No changes in viability or proliferation of the labeled cells were observed, and the secretome cytokine analysis indicated that the expression levels of 12 different proteins were not dysregulated by PBNP labeling. The optical properties of PBNPs were preserved postlabeling, suitable for the sensitive and quantitative detection of implanted cells. Labeled hMSCs exhibited strong photoacoustic contrast in vitro and in vivo when imaged at 730 nm, and the detection limit was 200 cells/µL in vivo. The photoacoustic signal increased as a function of cell concentration, indicating that the number of labeled cells can be quantified during and after cell transplantations. In hybrid ultrasound/photoacoustic imaging, this approach offers real-time and image-guided cellular injection even through an intact skull for brain intraparenchymal injections. Our labeling and imaging technique allowed the detection and monitoring of 5 × 104 mesenchymal stem cells in living mice over a period of 14 days.

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confidence: 99%

Photoacoustic Imaging of Human Mesenchymal Stem Cells Labeled with Prussian Blue–Poly(l-lysine) Nanocomplexes

et al. 2017

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“…This provides a quantitative measure of gold accumulation in fatty arteries of mice, that is, the greater the extension in gray scale unit, the higher the probability of gold accumulation. Here, gray scale values of voxels which lie between 0 and 140 suggest the presence of air; 140 and 231 suggest the presence of soft tissues and higher than 231 indicate the presence of high density matters . Table shows, in the 231 to 254 gray scale unit range (region of high density matter), that the mean voxel intensity of hyperlipidemic mice increases by 240% compared with normal mice.…”

Section: Resultsmentioning

confidence: 86%

Hyperlipidemic mice as a model for a real‐time in vivo detection of atherosclerosis by gold nanorods‐based diffusion reflection technique

Chakraborty

Ankri

Leshem-Lev

et al. 2018

Journal of Biophotonics

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Atherosclerosis (AS), the leading cause of morbidity and mortality in cardiovascular disease, needs an early detection for treatment and prevention of fatal events. Here, for the first time, we applied gold nanorods (GNRs)-assisted diffusion reflection (DR), a noninvasive technique for in vivo detection of AS in a high-fat-diet-induced c57bl mouse model, which resembles the manifestation of AS in humans. DR simply detects the change in light reflection profile of tissue due to the accumulation of GNRs in the AS plaques and enables clear detection of AS lesions in carotid and femoral arteries of these hyperlipidemic mice. After 24 hours post-GNRs injection, DR showed the highest efficiency of AS detection. Moreover, the sensitivity of the DR method is much higher than computed tomography (CT) and is comparable to ex vivo high-resolution CT. Our results strongly suggest that the DR method can detect early atherosclerotic lesions in a sensitive and specific manner.

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“…CT provides superior visualization of bone structures due to the inherent contrast between electron-dense bones and the more permeable surrounding soft tissues (Meir, Shamalov, et al, 2017;Shwartz et al, 2017). Therefore, CT has been used for cell tracking while combined with nanoparticles as labeling agents (Betzer et al, 2014;Betzer et al, 2015;Betzer, Meir, Motiei, Yadid, & Popovtzer, 2017;Betzer, Shilo, Motiei, & Popovtzer, 2019;Betzer, Shilo, et al, 2017;Hazkani et al, 2017;Meir, Betzer, et al, 2017;Meir, Betzer, Barnoy, Motiei, & Popovtzer, 2018;Popovtzer, 2014;Shilo et al, 2015;Shwartz et al, 2017).…”

Section: Tomographymentioning

confidence: 99%

Advances in imaging strategies for in vivo tracking of exosomes

Betzer

Barnoy

Sadan

et al. 2019

WIREs Nanomed Nanobiotechnol

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Exosomes have many biological functions as short‐ and long distance nanocarriers for cell‐to‐cell communication. They allow the exchange of complex information between cells, and thereby modulate various processes such as homeostasis, immune response and angiogenesis, in both physiological and pathological conditions. In addition, due to their unique abilities of migration, targeting, and selective internalization into specific cells, they are promising delivery vectors. As such, they provide a potentially new field in diagnostics and treatment, and may serve as an alternative to cell‐based therapeutic approaches. However, a major drawback for translating exosome treatment to the clinic is that current understanding of these endogenous vesicles is insufficient, especially in regards to their in vivo behavior. Tracking exosomes in vivo can provide important knowledge regarding their biodistribution, migration abilities, toxicity, biological role, communication capabilities, and mechanism of action. Therefore, the development of efficient, sensitive and biocompatible exosome labeling and imaging techniques is highly desired. Recent studies have developed different methods for exosome labeling and imaging, which have allowed for in vivo investigation of their bio‐distribution, physiological functions, migration, and targeting mechanisms. These improved imaging capabilities are expected to greatly advance exosome‐based nanomedicine applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Design principles for noninvasive, longitudinal and quantitative cell tracking with nanoparticle-based CT imaging

Cited by 56 publications

References 40 publications

Photoacoustic Imaging of Human Mesenchymal Stem Cells Labeled with Prussian Blue–Poly(l-lysine) Nanocomplexes

Photoacoustic Imaging of Human Mesenchymal Stem Cells Labeled with Prussian Blue–Poly(l-lysine) Nanocomplexes

Hyperlipidemic mice as a model for a real‐time in vivo detection of atherosclerosis by gold nanorods‐based diffusion reflection technique

Advances in imaging strategies for in vivo tracking of exosomes

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