Functionalized superparamagnetic iron oxide nanoparticles provide highly efficient iron-labeling in macrophages for magnetic resonance-based detection in vivo.
Cytotherapy
; 19(4): 555-569, 2017 04.
Article
in En
| MEDLINE
| ID: mdl-28214127
ABSTRACT
BACKGROUND AIMS:
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.METHODS:
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.RESULTS:
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.DISCUSSION:
A positively charged dextran-coated SPION is a promising tool to noninvasively track hepatic macrophage localization for therapeutic monitoring.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Magnetic Resonance Imaging
/
Dextrans
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Magnetite Nanoparticles
/
Cell Tracking
/
Iron
/
Macrophages
Type of study:
Diagnostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cytotherapy
Journal subject:
TERAPEUTICA
Year:
2017
Type:
Article
Affiliation country:
United kingdom