Abstract
Extracellular vesicles (EVs) are essential tools for conveying biological information and modulating functions of recipient cells. Implantation of isolated or modulated EVs can be innovative therapeutics for various diseases. Furthermore, EVs could be a biocompatible drug delivery vehicle to carry both endogenous and exogenous biologics. Tracking EVs should play essential roles in understanding the functions of EVs and advancing EV therapeutics. EVs have the characteristic structures consisting of the lipid bilayer and specific membrane proteins, through which they can be labeled efficiently. EVs can be labeled either directly using probes or indirectly by transfection of reporter genes. Optical imaging (fluorescent imaging and bioluminescent imaging), single-photon emission computed tomography (SPECT)/positron emission tomography (PET), and magnetic resonance imaging (MRI) are currently used for imaging EVs. Labeling EVs with superparamagnetic iron oxide (SPIO) nanoparticles for MRI tracking is a promising method that can be translated into clinic. SPIO can be internalized by most of the cell types and then released as SPIO containing EVs, which can be visualized on T2*-weighted imaging. However, this method has limitations in real-time imaging because of the life cycle of SPIO after EV degradation. Further studies will be needed to validate SPIO labeling by other imaging modalities in preclinical studies. The emerging technologies of labeling and imaging EVs with SPIO in comparison with other imaging modalities are reviewed in this paper.
Highlights
Extracellular vesicles (EVs), which represent microvesicle and exosome secretomes, are produced by most of the cell types under physiological and pathological conditions, playing essential roles in intercellular communications
EVs secreted from cells migrate through interstitial fluid or systemic circulation and transfer their cargos consisting of nucleic acids, proteins, lipids, and mitochondrial fractions to their recipient cells [1,2,3]. mRNAs from EVs can be translated in the recipient cells and miRNA from EVs can modulate gene expression and biological functions [4]
Myocardial function is modified by those interstitial cell-derived EVs in adaptive responses both in beneficial or harmful ways. miR-21*, transferred from fibroblast-derived EVs stimulates myocardial hypertrophy [5]
Summary
Extracellular vesicles (EVs), which represent microvesicle and exosome secretomes, are produced by most of the cell types under physiological and pathological conditions, playing essential roles in intercellular communications. Mesenchymal stem cell (MSC)-derived EVs reduced myocardial infarct size following the ischemia reperfusion in animal models [8,9] Due to their unique characteristics including nano-scale size, biogenesis potential, endogenous lipid bilayer membrane, signal transduction system, and effectors of various biological information, EVs can be useful in numerous ways in diagnostic and therapeutic roles. With higher biocompatibility and less toxicity, EVs may replace artificial lipid nanoparticles in the future as drug delivery vehicles to deliver exogenous and endogenous therapeutic cargos Due to these potentials of EVs, monitoring the distribution and fate of secreted or implanted EVs in vitro or in vivo is one of the essential strategies in understanding their functions and advancing the EV-mediated diagnostics or therapeutics. We review the emerging technologies of labeling and imaging EV with SPIO and compare them with other imaging modalities
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