Functionalized superparamagnetic iron oxide nanoparticles provide highly efficient iron-labeling in macrophages for magnetic resonance-based detection in vivo.



Sharkey, J ORCID: 0000-0002-0516-7622, Starkey Lewis, PJ, Barrow, M, Alwahsh, SM, Noble, J, Livingstone, E, Lennen, RJ, Jansen, MA, Carrion, JG, Liptrott, N ORCID: 0000-0002-5980-8966
et al (show 8 more authors) (2017) Functionalized superparamagnetic iron oxide nanoparticles provide highly efficient iron-labeling in macrophages for magnetic resonance-based detection in vivo. Cytotherapy, 19 (4). 555 - 569.

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Abstract

Tracking cells during regenerative cytotherapy is crucial for monitoring their safety and efficacy. Macrophages are an emerging cell-based regenerative therapy for liver disease and can be readily labeled for medical imaging. A reliable, clinically applicable cell-tracking agent would be a powerful tool to study cell biodistribution.Using a recently described chemical design, we set out to functionalize, optimize and characterize a new set of superparamagnetic iron oxide nanoparticles (SPIONs) to efficiently label macrophages for magnetic resonance imaging-based cell tracking in vivo.A series of cell health and iron uptake assays determined that positively charged SPIONs (+16.8 mV) could safely label macrophages more efficiently than the formerly approved ferumoxide (-6.7 mV; Endorem) and at least 10 times more efficiently than the clinically approved SPION ferumoxytol (-24.2 mV; Rienso). An optimal labeling time of 4 h at 25 µg/mL was demonstrated to label macrophages of mouse and human origin without any adverse effects on cell viability whilst providing substantial iron uptake (>5 pg Fe/cell) that was retained for 7 days in vitro. SPION labeling caused no significant reduction in phagocytic activity and a shift toward a reversible M1-like phenotype in bone marrow-derived macrophages (BMDMs). Finally, we show that SPION-labeled BMDMs delivered via the hepatic portal vein to mice are localized in the hepatic parenchyma resulting in a 50% drop in T2* in the liver. Engraftment of exogenous cells was confirmed via immunohistochemistry up to 3 weeks posttransplantation.A positively charged dextran-coated SPION is a promising tool to noninvasively track hepatic macrophage localization for therapeutic monitoring.

Item Type: Article
Uncontrolled Keywords: cell therapy, cell tracking, liver fibrosis, macrophage, MRI
Depositing User: Symplectic Admin
Date Deposited: 23 Feb 2017 10:46
Last Modified: 23 Nov 2020 21:15
DOI: 10.1016/j.jcyt.2017.01.003
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3006010