Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for cell graft monitoring and quantitation.
OBJECTIVE
To perform a quantitative analysis of anionic maghemite nanoparticle-labeled cells in vitro and determine the effect of labeling on signal intensity at magnetic resonance (MR) imaging.


METHODS
The study was approved by the institutional animal care and use committee at Hôpital Bichat. In vitro cell proliferation, iron content per cell, and MR signal intensity of cells were measured in agarose phantoms for 0-14 days of culture after labeling of rat smooth muscle cells with anionic maghemite nanoparticles. Next, iron oxide-labeled smooth muscle cells were injected into healthy hearts and hearts with ischemic injury in seven live Fisher rats. Ex vivo MR imaging experiments in excised hearts 2 and 48 hours after injection were performed with a 1.5-T medical imaging system by using T2-weighted gradient-echo and spin-echo sequences. Histologic sections were obtained after MR imaging. Correlation analyses between division factor of iron load and cell amplification factor and between 1/T2 and number of labeled cells or number of days in culture were performed by using linear regression.


RESULTS
Viability of smooth muscle cells was not affected by magnetic labeling. Transmission electron micrographs of cells revealed the presence of iron oxide nanoparticles in vesicles up to day 14 of culture. Intracellular iron concentration decreased in parallel with cell division (r2 = 0.99) and was correlated with MR signal intensity (r2 = 0.95). T2*-weighted MR images of excised rat hearts showed hypointense signal in myocardium at 2 and 48 hours after local injection of labeled cells. Subsequent histologic staining evidenced iron oxide nanoparticles within cells and confirmed the presence of the original cells at 2 and 48 hours after implantation.


CONCLUSIONS
Magnetic labeling of smooth muscle cells with anionic maghemite nanoparticles allows detection of cells with MR imaging after local transplantation in the heart.
Rivière
Charlotte
C
Laboratoire des Milieux Désordonnés et Hétérogènes and Laboratoire des Liquides Ioniques et Interfaces Chargées, Université Pierre et Marie Curie, Paris, France.
Boudghène
Frank P
FP
Gazeau
Florence
F
Roger
Jacky
J
Pons
Jean-Noël
JN
Laissy
Jean-Pierre
JP
Allaire
Eric
E
Michel
Jean-Baptiste
JB
Letourneur
Didier
D
Deux
Jean-François
JF
D000818:Animals; D006348:Cardiac Surgical Procedures; D002452:Cell Count; D002470:Cell Survival; D017690:Cell Transplantation / Q000473:pathology*; D002478:Cells, Cultured; D005290:Ferric Compounds; D008279:Magnetic Resonance Imaging; D009130:Muscle, Smooth / Q000166:cytology*; D009206:Myocardium / Q000473:pathology*; D049329:Nanostructures; D051381:Rats; D011916:Rats, Inbred F344; D013194:Staining and Labeling
D005290:Ferric Compounds; C000499:ferric oxide