title: Can magnetic targeting of magnetically labeled circulating cells optimize intramyocardial cell retention?
abstract: Therapeutic intracavitary stem cell infusion currently suffers from poor myocardial homing. We examined whether cardiac cell retention could be enhanced by magnetic targeting of endothelial progenitor cells (EPCs) loaded with iron oxide nanoparticles. EPCs were magnetically labeled  with citrate-coated iron oxide nanoparticles. Cell proliferation, migration, and CXCR4 chemokine receptor expression were assessed in different labeling conditions and no adverse effects of the magnetic label were observed. The magnetophoretic mobility of labeled EPCs was determined in vitro,  with the same magnet as that subsequently used in vivo. Coronary artery occlusion was induced for 30 min in 36 rats (31 survivors), followed by 20 min of reperfusion. The rats were randomized to receive, during brief aortic cross-clamping, direct intraventricular injection of culture medium  (n = 7) or magnetically labeled EPCs (n = 24), with (n = 14) or without (n = 10) subcutaneous insertion of a magnet over the chest cavity (n = 14). The hearts were explanted 24 h later and engrafted cells were visualized by magnetic resonance imaging (MRI)  of the heart at 1.5 T. Their abundance in the myocardium was also analyzed semiquantitatively by immunofluorescence, and quantitatively by real-time polymerase chain reaction (RT-PCR).Although differences in cell retention between groups failed to be statistically significant using RT-PCR  quantification, due to the variability of the animal model, immunostaining showed that the average number of engrafted EPCs was significantly ten times higher with than without magnetic targeting. There was thus a consistent trend favoring the magnet-treated hearts, thereby suggesting magnetic  targeting as a potentially new mean of enhancing myocardial homing of intravascularly delivered stem cells. Magnetic targeting has the potential to enhance myocardial retention of intravascularly delivered endothelial progenitor cells.
authors.affiliation: INSERM U633, Laboratory of Surgical Research, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chaudeurge
authors.forename: Claire
authors.initials: C
authors.lastname: Wilhelm
authors.forename: Annabel
authors.initials: A
authors.lastname: Chen-Tournoux
authors.forename: Patrick
authors.initials: P
authors.lastname: Farahmand
authors.forename: Valérie
authors.initials: V
authors.lastname: Bellamy
authors.forename: Gwennhael
authors.initials: G
authors.lastname: Autret
authors.forename: Christine
authors.initials: C
authors.lastname: Ménager
authors.forename: Albert
authors.initials: A
authors.lastname: Hagège
authors.forename: Jerome
authors.initials: J
authors.lastname: Larghéro
authors.forename: Florence
authors.initials: F
authors.lastname: Gazeau
authors.forename: Olivier
authors.initials: O
authors.lastname: Clément
authors.forename: Philippe
authors.initials: P
authors.lastname: Menasché
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D009206:Myocardium; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide