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Nanomedicine. 2018 Nov 16. pii: S1549-9634(18)30552-5. doi: 10.1016/j.nano.2018.10.014. [Epub ahead of print]

Improved cellular uptake of perfluorocarbon nanoparticles for in vivo murine cardiac 19F MRS/MRI and temporal tracking of progenitor cells.

Author information

1
Radcliffe Department of Medicine, Wellcome Centre for Human Genetics; Department of Cardiovascular Medicine, Wellcome Centre for Human Genetics. Electronic address: Christakis.Constantinides@gmail.com.
2
Radcliffe Department of Medicine, Wellcome Centre for Human Genetics; Department of Cardiovascular Medicine, Wellcome Centre for Human Genetics.
3
Division of Structural Biology, University of Oxford, Henry Wellcome Building for Genomic Medicine, Headington, Oxford, UK; Wellcome Centre for Human Genetics, Cellular Imaging Core, University of Oxford, Oxford.
4
Radboud University Medical Center (Radboud UMC), Department of Tumor Immunology, 278, Radboud Institute for Molecular Life Sciences (RIMLS), Postbox 9101, Nijmegen, The Netherlands.
5
Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
6
Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics and The Cyprus School of Molecular Medicine, Nicosia, Cyprus.

Abstract

Herein, we maximize the labeling efficiency of cardiac progenitor cells (CPCs) using perfluorocarbon nanoparticles (PFCE-NP) and 19F MRI detectability, determine the temporal dynamics of single-cell label uptake, quantify the temporal viability/fluorescence persistence of labeled CPCs in vitro, and implement in vivo, murine cardiac CPC MRI/tracking that could be translatable to humans. FuGENEHD-mediated CPC PFCE-NP uptake is confirmed with flow cytometry/confocal microscopy. Epifluorescence imaging assessed temporal viability/fluorescence (up to 7 days [D]). Nonlocalized murine 19F MRS and cardiac MRI studied label localization in terminal/longitudinal tracking studies at 9.4 T (D1-D8). A 4-8 fold 19F concentration increase is evidenced in CPCs for FuGENE vs. directly labeled cells. Cardiac 19F signals post-CPC injections diminished in vivo to ~31% of their values on D1 by D7/D8. Histology confirmed CPC retention, dispersion, and macrophage-induced infiltration. Intra-cardiac injections of PFCE-NP-labeled CPCs with FuGENE can be visualized/tracked in vivo for the first time with 19F MRI.

KEYWORDS:

Cardiac stem cells; Fluorine MRI; Macrophages; Perfluorocarbon nanoparticles; Tracking

PMID:
30448526
DOI:
10.1016/j.nano.2018.10.014

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