Tracking Exosomes by Magnetic Resonance Imaging

Exosomes are cell-derived nanovesicles that transmit molecular signals associated with normal physiological and disease processes. Tracking the biodistribution of endogenous exosomes is essential for understanding exosome pathogenesis and utilizing exosomes as effective diagnostic and therapeutic vectors. Magnetic resonance imaging (MRI) has been widely used among the tracking methods used for this purpose in recent years.

What is MRI Technology?

MRI is an attractive imaging modality widely used in clinical practice and has excellent soft tissue contrast without ionizing radiation. MRI uses magnetic resonance to acquire electromagnetic signals from the body and reconstruct the information about them, offering the advantages of non-invasive radiation and high spatial and soft tissue resolution. Magnetic labeling of exosomes allows for in vivo tracking and visualization using MRI to follow the distribution and fate of exosomes over time.

Figure 1. Visualization of mouse melanoma cell B16-derived exosomes by MRI. (Liu T, et al., 2022)

What is the Principle of MRI?

MRI is a biomagnetic nuclear spin imaging technique that has developed rapidly with the development of computer technology, electronic circuit technology, and superconductor technology. It is the use of magnetic fields and radiofrequency pulses to make the hydrogen nucleus (H +) in the tissue into the action of the chapter action to produce radiofrequency signals, computer processing, and imaging. Atomic nucleus in the in-motion, absorption and atomic nucleus in-motion frequency of the same radio frequency pulse, the atomic nucleus resonance absorption occurs, after removing the radio frequency pulse, the atomic nucleus magnetic moment and a part of the absorbed energy in the form of electromagnetic waves emitted, known as resonance emission. When the labeled exosome is placed in a magnetic field, irradiated with appropriate electromagnetic waves, and the electromagnetic waves it releases are analyzed, the location of the exosome can be learned.

What are the Commonly Used Contrast Agents for Tracking Exosomes by MRI?

Iron oxide nanoparticles (IONPs) are widely used in biomedical research and clinical applications, including MRI, drug delivery, and disease treatment. γ-Fe₂O₃ and Fe₃O₄ nanoparticles have the advantages of biocompatibility and biodegradability. They can be used to label cells and extracellular vesicles (EVs), and they can be tracked and visualized by MRI to ensure that they reach their target sites in vivo and are retained in the tissue. MRI tracking with superparamagnetic iron oxide nanoparticles (SPION) labeled exosomes is a promising approach that can be translated to the clinic. Due to their small size and biocompatibility, SPION and ultra-small superparamagnetic iron oxide nanoparticles (USPION) are attractive probes for exosome labeling and MRI tracking in vivo. In recent years, scientists have also used gadolinium, gold iron oxide nanoparticles (GION), and ferritin heavy chain (FTH1) as contrast agents for MRI tracking of exosomes.

Figure 2. Schematic of SPION labeling method. (Tada Y, et al., 2019)

Application Examples of Tracking Exosomes by MRI

Human stem cell-derived EVs are currently being researched for cell-free healing in regenerative medicine applications. Researchers labeled EVs with magnetic nanoparticles to create magnetic EVs that can be tracked by MRI. SPION is coated with a polyhistidine tag that purifies the labeled EVs by efficiently removing unencapsulated SPIO from the solution. The biodistribution of systemically injected human induced pluripotent stem cell (iPSC)-derived magnetic EVs was evaluated in three different animal models of kidney injury and myocardial ischemia. The research found that magnetic EVs could selectively localize to the site of injury and provide substantial protection in the kidney injury model. In vivo MRI tracking of magnetically labeled EVs represents a novel approach to assess and quantify their distribution and may help optimize the further development of EV-based cell-free therapies.

Figure 3. MRI of iPSC-EV uptake in a kidney model. (Han Z, et al., 2021)

Researchers designed a fusion protein consisting of ferritin heavy chain (FTH1) and truncated lactadherin. FTH1 is used as an MRI reporter, and lactadherin is a transmembrane protein located on the outer surface of exosomes. Infection of mesenchymal stem cells with lentivirus carrying fusion proteins and isolation of exosomes from labeled cells by ultracentrifugation. Validation of labeled exosomes by transmission electron microscopy (TEM), western blotting, nanoparticle tracking analysis (NTA), and tracking by MRI. The research found that the characteristics of FTH-labeled exosomes remained comparable to those of unlabeled. MRI showed that FTH1-labeled exosomes could be visualized in vitro and in vivo.

Figure 4. MRI reveals the presence of exosomal MSC/FTH1 in muscle tissue. (Liu T, et al., 2020)

Our Services and Products

Based on years of experience, Creative Biostructure provides one-stop exosome services, including exosome isolation, characterization, labeling, tracking, targeting, and functional analysis to satisfy clients' diverse requirements. In addition to comprehensive exosome services, we offer a range of high-quality exosome products to help clients explore the potential of exosomes in cancer diagnostic/therapy and as drug carriers.

If you are interested in our exosome services and products, please feel free to contact us for more details.

References

1. Liu T, et al. In vivo visualization of murine melanoma cells B16-derived exosomes through magnetic resonance imaging. Biochim Biophys Acta Gen Subj. 2022. 1866(2): 130062.
2. Tada Y, C. Yang P. Iron Oxide Labeling and Tracking of Extracellular Vesicles. Magnetochemistry. 2019. 5(4): 60.
3. Han Z, et al. Highly efficient magnetic labeling allows MRI tracking of the homing of stem cell-derived extracellular vesicles following systemic delivery. J Extracell Vesicles. 2021. 10(3): e12054.
4. Liu T, et al. Visualization of exosomes from mesenchymal stem cells in vivo by magnetic resonance imaging. Magn Reson Imaging. 2020. 68: 75-82.
5. Chen Y, Hou S. Recent progress in the effect of magnetic iron oxide nanoparticles on cells and extracellular vesicles. Cell Death Discov. 2023. 9(1): 195.
6. Jiang A, et al. In Vivo Imaging for the Visualization of Extracellular Vesicle-Based Tumor Therapy. ChemistryOpen. 2022. 11(9): e202200124.