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Quantitative Magnetic Particle Imaging Monitors the Transplantation, Biodistribution, and Clearance of Stem Cells In Vivo
Open accessAbstract
Stem cell therapies have enormous potential for treating many debilitating diseases, including heart failure, stroke and traumatic brain injury. For maximal efficacy, these therapies require targeted cell delivery to specific tissues followed by successful cell engraftment. However, targeted delivery remains an open challenge. As one example, it is common for intravenous deliveries of mesenchymal stem cells (MSCs) to become entrapped in lung microvasculature instead of the target tissue. Hence, a robust, quantitative imaging method would be essential for developing efficacious cell therapies. Here we show that Magnetic Particle Imaging (MPI), a novel technique that directly images iron-oxide nanoparticle-tagged cells, can longitudinally monitor and quantify MSC administration in vivo. MPI offers near-ideal image contrast, depth penetration, and robustness; these properties make MPI both ultra-sensitive and linearly quantitative. Here, we imaged, for the first time, the dynamic trafficking of intravenous MSC administrations using MPI. Our results indicate that labeled MSC injections are immediately entrapped in lung tissue and then clear to the liver within one day, whereas standard iron oxide particle (Resovist) injections are immediately taken up by liver and spleen. Longitudinal MPI-CT imaging also indicated a clearance half-life of MSC iron oxide labels in the liver at 4.6 days. Finally, our ex vivo MPI biodistribution measurements of iron in liver, spleen, heart, and lungs after injection showed excellent agreement (R(2) = 0.943) with measurements from induction coupled plasma spectrometry. These results demonstrate that MPI offers strong utility for noninvasively imaging and quantifying the systemic distribution of cell therapies and other therapeutic agents.
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Tomographic Magnetic Particle Imaging With a Single-Sided Field-Free Line Scanner
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“However, MPI technology has considerable potential to surpass existing in-vivo imaging modalities in certain clinical applications, such as angiography [4], [5], cancer screening [6], [7], functional imaging [8], cell tracking [9], [10], and drug delivery [11], [12].”
Genetically encoded iron‐associated proteins as MRI reporters for molecular and cellular imaging
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A theranostic platform for localized magnetic fluid hyperthermia and magnetic particle imaging
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“5 mm.(13,20) In general, tradeoffs exist between resolution, signal-to-noise ratio (SNR), and system parameters such as gradient strength and acquisition speed.”
BackgroundRapid Analysis of Cell–Nanoparticle Interactions using Single‐Cell Raman Trapping Microscopy
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Nanotechnology in Immunotherapy for Type 1 Diabetes: Promising Innovations and Future Advances
Nigam, S., Bishop, J. O., Hayat, H., Quadri, T., Hayat, H., & Wang, P. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030644 · Cited by 13
Mechanisms of Potential Therapeutic Utilization of Mesenchymal Stem Cells in COVID-19 Treatment
Fang, Y., Lao, P., Tang, L., Chen, J., Chen, Y., Sun, L., Tan, W., & Fan, X. (2023) · Cell Transplantation · doi:10.1177/09636897231184611 · Cited by 13
Detection and Compensation of Periodic Motion in Magnetic Particle Imaging
Gdaniec, N., Schlüter, M., Möddel, M., Kaul, M. G., Krishnan, K. M., Schlaefer, A., & Knopp, T. (2017) · IEEE Transactions on Medical Imaging · doi:10.1109/tmi.2017.2666740 · Cited by 13
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Magnetic particle imaging deblurring with dual contrastive learning and adversarial framework
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Sato, N., & Choyke, P. L. (2021) · Molecular Imaging and Biology · doi:10.1007/s11307-021-01669-y · Cited by 12
“Tracking SPIO-labeled human MSCs [47] and T cells [48] administered to mice has been performed.”
BackgroundFicko, B. W., Ndong, C., Giacometti, P., Griswold, K. E., & Diamond, S. G. (2016) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2016.2584241 · Cited by 12
“[8], cell tagging [9], [10], drug targeting [11], DNA detection [12], assay measurement [13]–[18], multi-MNP tracer systems [19], [20], health monitoring [21], temperature measurement [22]–[24], stem cell tracking [25], [26], and detection of plant viruses [27].”
BackgroundMurase, K. (2020) · Medical Physics · doi:10.1002/mp.14056 · Cited by 12
Image-Guided Thermal Therapy Using Magnetic Particle Imaging and Magnetic Fluid Hyperthermia
Dhavalikar, R., Bohórquez, A. C., & Rinaldi, C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813928-8.00010-7 · Cited by 13
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“For this reason, calibration samples may be imaged in separate image(s) [6, 10, 24, 25], and in this paper, we refer to this as “external calibration.””
BackgroundMixing-Space Magnetic Particle Imaging
Zhang, R., Sun, S., Sun, S., Meribout, M., Xu, L., & Zhong, J. (2024) · IEEE Transactions on Instrumentation and Measurement · doi:10.1109/tim.2024.3500075 · Cited by 11
“M AGNETIC particle imaging (MPI) is a new imaging modality that has shown great promise in biomedical applications [1], [2], including vascular imaging [3], [4], cell tracking [5], [6], [7], drug delivery [8], and magnetic hyper-thermia [9].”
Innovative nanotechnology tools for the functional control and tracking of human stem cells
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Probing particle-matrix interactions during magnetic particle spectroscopy
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A cost-effective magnetic particle imaging scanner based on mixing-frequency spectra
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McDonough, C., Pagan, J., & Tonyushkin, A. (2022) · Physics in Medicine and Biology · doi:10.1088/1361-6560/aca5ec · Cited by 10
“MPI holds great promise to surpass existing in vivo imaging modalities in certain clinical applications, such as angiographyWeizenecker et al (2009), cancer screening (Yu et al 2017), functional imaging (Cooley et al 2018), and cell tracking (Zheng et al 2015, 2016, Bulte et al 2015).”
BackgroundIn Vivo Stem Cell Imaging Principles and Applications
Hong, S., Lee, D.-S., Bae, G.-W., Jeon, J., Kim, H. K., Rhee, S., & Jung, K. O. (2023) · International Journal of Stem Cells · doi:10.15283/ijsc23045 · Cited by 10
“MPI could produce millimeter-scale resolution, high sensitivity, and high contrast angiographic images (33).”
BackgroundTake a Deep Breath - Monitoring of Inhaled Nanoparticles with Magnetic Particle Imaging
Wegner, F., Buzug, T. M., & Barkhausen, J. (2018) · Theranostics · doi:10.7150/thno.27454 · Cited by 10
“Furthermore, stem cells [15,18] as well as cancer cells [19] can be tracked by MPI.”
Advancement of magnetic particle imaging in diagnosis and therapy
Harini, K., Girigoswami, K., Pallavi, P., Gowtham, P., Prabhu, A. D., & Girigoswami, A. (2024) · Advances in Natural Sciences: Nanoscience and Nanotechnology · doi:10.1088/2043-6262/ad3b7a · Cited by 8
Magnet‐Bead Based MicroRNA Delivery System to Modify CD133+ Stem Cells
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“In addition, cells which are magnetically labeled can be tracked and monitored using magnetic resonance imaging (MRI) [33] or the novel imaging modality magnetic particle imaging (MPI) [34, 35].”
BackgroundTaylor, S. D., Serpa, P. B. S., dos Santos, A. P., Hart, K. A., Vaughn, S. A., Moore, G. E., Mukhopadhyay, A., & Page, A. E. (2022) · Journal of Veterinary Internal Medicine · doi:10.1111/jvim.16447 · Cited by 9
“Molecular imaging technologies have been used in rodent models to track the fate of IV injected MSC, 80% of which become trapped in lung microvasculature within 1 hour of injection due to the relatively large size of MSC.(54-60) In rodents and dogs, pulmonary embolism and myocardial infarction occur after intra-arteri…”
Method
Metadata
- Authors
- Zheng, B., von See, M. P., Yu, E., Gunel, B., Lu, K., Vazin, T., Schaffer, D. V., Goodwill, P. W., & Conolly, S. M.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Zheng, Bo
- ORCID
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2016
- Volume
- 6
- Issue
- 3
- Pages
- 291-301
- ISSN
- 1838-7640 (ISSN-L)
- PMC
- PMC4737718
- OpenAlex
- W2275153700
- Cited by
- 322
- References
- 53
- Citations by year
- 2026: 18 · 2025: 25 · 2024: 29 · 2023: 36 · 2022: 37 · 2021: 35 · 2020: 34 · 2019: 30 · 2018: 30 · 2017: 35 · 2016: 13
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Theranostics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- tub.dok (Hamburg University of Technology) (submittedVersion, cc-by-nc)
- TUHH Open Research
- Funders
- W. M. Keck Foundation (009323)
- ACT Government
- Siebel Scholars Foundation
- National Institutes of Health (009323, NIH-R01)
- National Institute of Mental Health (R24MH106053)
- National Institute of Biomedical Imaging and Bioengineering (R01EB019458, R01EB013689)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- magnetic particle imaging, mesenchymal stem cells, stem cell transplantation, cell biodistribution, cell clearance, stem cell therapy
- MeSH terms
- Animals, Diagnostic Imaging, Female, Ferric Compounds, Humans, Magnetics, Rats, Inbred F344, Staining and Labeling, Tissue Distribution, Mesenchymal Stem Cell Transplantation, Mice, Nanoparticles, Administration, Intravenous
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