PMID- 28214127
OWN - NLM
STAT- MEDLINE
DCOM- 20170802
LR  - 20220330
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Print)
IS  - 1465-3249 (Linking)
VI  - 19
IP  - 4
DP  - 2017 Apr
TI  - Functionalized superparamagnetic iron oxide nanoparticles provide highly 
      efficient iron-labeling in macrophages for magnetic resonance-based detection in 
      vivo.
PG  - 555-569
LID - S1465-3249(17)30005-1 [pii]
LID - 10.1016/j.jcyt.2017.01.003 [doi]
AB  - 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 microg/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.
CI  - Copyright (c) 2017 International Society for Cellular Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Sharkey, Jack
AU  - Sharkey J
AD  - Department of Cellular and Molecular Physiology, Institute of Translational 
      Medicine, University of Liverpool, Liverpool, United Kingdom; UK Regenerative 
      Medicine Platform Safety and Efficacy Hub, United Kingdom.
FAU - Starkey Lewis, Philip J
AU  - Starkey Lewis PJ
AD  - UK Regenerative Medicine Platform Safety and Efficacy Hub, United Kingdom; MRC 
      Centre for Regenerative Medicine, Little France Drive, University of Edinburgh, 
      Edinburgh, United Kingdom.
FAU - Barrow, Michael
AU  - Barrow M
AD  - UK Regenerative Medicine Platform Safety and Efficacy Hub, United Kingdom; 
      Department of Chemistry, University of Liverpool, Liverpool, United Kingdom.
FAU - Alwahsh, Salamah M
AU  - Alwahsh SM
AD  - MRC Centre for Regenerative Medicine, Little France Drive, University of 
      Edinburgh, Edinburgh, United Kingdom.
FAU - Noble, June
AU  - Noble J
AD  - Cardiovascular Sciences, Queens Medical Research Institute, University of 
      Edinburgh, Edinburgh, United Kingdom.
FAU - Livingstone, Eilidh
AU  - Livingstone E
AD  - MRC Centre for Regenerative Medicine, Little France Drive, University of 
      Edinburgh, Edinburgh, United Kingdom.
FAU - Lennen, Ross J
AU  - Lennen RJ
AD  - Edinburgh Preclinical Imaging, University of Edinburgh, Edinburgh, United 
      Kingdom.
FAU - Jansen, Maurits A
AU  - Jansen MA
AD  - Edinburgh Preclinical Imaging, University of Edinburgh, Edinburgh, United 
      Kingdom.
FAU - Carrion, Jaime Garcia
AU  - Carrion JG
AD  - Department of Chemistry, University of Liverpool, Liverpool, United Kingdom.
FAU - Liptrott, Neill
AU  - Liptrott N
AD  - MRC Centre for Drug Safety Science, Ashton Street, University of Liverpool, 
      Liverpool, United Kingdom; European Nanomedicine Characterisation Laboratory 
      (EU-NCL), Department of Molecular and Clinical Pharmacology, University of 
      Liverpool, Liverpool, United Kingdom.
FAU - Forbes, Shareen
AU  - Forbes S
AD  - Cardiovascular Sciences, Queens Medical Research Institute, University of 
      Edinburgh, Edinburgh, United Kingdom.
FAU - Adams, Dave J
AU  - Adams DJ
AD  - UK Regenerative Medicine Platform Safety and Efficacy Hub, United Kingdom; 
      Department of Chemistry, University of Liverpool, Liverpool, United Kingdom.
FAU - Chadwick, Amy E
AU  - Chadwick AE
AD  - UK Regenerative Medicine Platform Safety and Efficacy Hub, United Kingdom; MRC 
      Centre for Drug Safety Science, Ashton Street, University of Liverpool, 
      Liverpool, United Kingdom.
FAU - Forbes, Stuart J
AU  - Forbes SJ
AD  - UK Regenerative Medicine Platform Safety and Efficacy Hub, United Kingdom; MRC 
      Centre for Regenerative Medicine, Little France Drive, University of Edinburgh, 
      Edinburgh, United Kingdom.
FAU - Murray, Patricia
AU  - Murray P
AD  - Department of Cellular and Molecular Physiology, Institute of Translational 
      Medicine, University of Liverpool, Liverpool, United Kingdom; UK Regenerative 
      Medicine Platform Safety and Efficacy Hub, United Kingdom.
FAU - Rosseinsky, Matthew J
AU  - Rosseinsky MJ
AD  - UK Regenerative Medicine Platform Safety and Efficacy Hub, United Kingdom; 
      Department of Chemistry, University of Liverpool, Liverpool, United Kingdom.
FAU - Goldring, Christopher E
AU  - Goldring CE
AD  - UK Regenerative Medicine Platform Safety and Efficacy Hub, United Kingdom; MRC 
      Centre for Drug Safety Science, Ashton Street, University of Liverpool, 
      Liverpool, United Kingdom. Electronic address: chrissy@liverpool.ac.uk.
FAU - Park, B Kevin
AU  - Park BK
AD  - UK Regenerative Medicine Platform Safety and Efficacy Hub, United Kingdom; MRC 
      Centre for Drug Safety Science, Ashton Street, University of Liverpool, 
      Liverpool, United Kingdom.
LA  - eng
GR  - MR/K017047/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/K026739/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/L012707/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20170215
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 0 (Dextrans)
RN  - 0 (Magnetite Nanoparticles)
RN  - E1UOL152H7 (Iron)
RN  - G6N3J05W84 (ferumoxides)
RN  - XM0M87F357 (Ferrosoferric Oxide)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology/metabolism
MH  - Bone Marrow Transplantation/methods
MH  - Cell Survival
MH  - Cell Tracking/*methods
MH  - Cells, Cultured
MH  - Dextrans/*chemistry/pharmacokinetics
MH  - Ferrosoferric Oxide/chemistry/pharmacokinetics
MH  - Humans
MH  - Iron/*metabolism
MH  - Liver Cirrhosis/therapy
MH  - Macrophages/*cytology/*metabolism
MH  - Magnetic Resonance Imaging/*methods
MH  - Magnetite Nanoparticles/*chemistry
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Tissue Distribution
PMC - PMC5357746
OTO - NOTNLM
OT  - MRI
OT  - cell therapy
OT  - cell tracking
OT  - liver fibrosis
OT  - macrophage
EDAT- 2017/02/19 06:00
MHDA- 2017/08/03 06:00
PMCR- 2017/04/01
CRDT- 2017/02/19 06:00
PHST- 2016/06/30 00:00 [received]
PHST- 2016/12/01 00:00 [revised]
PHST- 2017/01/02 00:00 [accepted]
PHST- 2017/02/19 06:00 [pubmed]
PHST- 2017/08/03 06:00 [medline]
PHST- 2017/02/19 06:00 [entrez]
PHST- 2017/04/01 00:00 [pmc-release]
AID - S1465-3249(17)30005-1 [pii]
AID - 10.1016/j.jcyt.2017.01.003 [doi]
PST - ppublish
SO  - Cytotherapy. 2017 Apr;19(4):555-569. doi: 10.1016/j.jcyt.2017.01.003. Epub 2017 
      Feb 15.