TY - JOUR
T1 - Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium
AU - Amsalem, Yoram
AU - Mardor, Yael
AU - Feinberg, Micha S.
AU - Landa, Natalie
AU - Miller, Liron
AU - Daniels, Dianne
AU - Ocherashvilli, Aharon
AU - Holbova, Radka
AU - Yosef, Orna
AU - Barbash, Israel M.
AU - Leor, Jonathan
PY - 2007/9
Y1 - 2007/9
N2 - BACKGROUND - Cell labeling with superparamagnetic iron oxide (SPIO) nanoparticles enables noninvasive MRI and tracking of transplanted stem cells. We sought to determine whether mesenchymal stem cell (MSC) outcome is affected by SPIO labeling in a rat model of myocardial infarction. METHODS AND RESULTS - Rat MSCs were labeled with SPIO (ferumoxides; Endorem; Guerbet, Villepinte, France). By trypan-blue exclusion assay, almost 100% of the cells remained viable after labeling. Seven days after MI, rats were randomized to injections of 2×10 SPIO-labeled MSCs, 2×10 unlabeled MSCs, or saline. Labeled cells were visualized in the infarcted myocardium as large black spots by serial MRI studies throughout the 4-week follow-up. The presence of labeled cells was confirmed by iron staining and real-time polymerase chain reaction on postmortem specimens. At 4 weeks after transplantation, the site of cell injection was infiltrated by inflammatory cells. Costaining for iron and ED1 (resident macrophage marker) showed that the iron-positive cells were cardiac macrophages. By real-time polymerase chain reaction, the Y-chromosome-specific SRY DNA of MSCs from male donors was not detected in infarcted hearts of female recipients. Serial echocardiography studies at baseline and 4 weeks after cell transplantation showed that both unlabeled and labeled MSCs attenuated progressive left ventricular dilatation and dysfunction compared with controls. CONCLUSIONS - At 4 weeks after transplantation of SPIO-labeled MSCs, the transplanted cells are not present in the scar and the enhanced MRI signals arise from cardiac macrophages that engulfed the SPIO nanoparticles. However, both labeled and unlabeled cells attenuate left ventricular dilatation and dysfunction after myocardial infarction.
AB - BACKGROUND - Cell labeling with superparamagnetic iron oxide (SPIO) nanoparticles enables noninvasive MRI and tracking of transplanted stem cells. We sought to determine whether mesenchymal stem cell (MSC) outcome is affected by SPIO labeling in a rat model of myocardial infarction. METHODS AND RESULTS - Rat MSCs were labeled with SPIO (ferumoxides; Endorem; Guerbet, Villepinte, France). By trypan-blue exclusion assay, almost 100% of the cells remained viable after labeling. Seven days after MI, rats were randomized to injections of 2×10 SPIO-labeled MSCs, 2×10 unlabeled MSCs, or saline. Labeled cells were visualized in the infarcted myocardium as large black spots by serial MRI studies throughout the 4-week follow-up. The presence of labeled cells was confirmed by iron staining and real-time polymerase chain reaction on postmortem specimens. At 4 weeks after transplantation, the site of cell injection was infiltrated by inflammatory cells. Costaining for iron and ED1 (resident macrophage marker) showed that the iron-positive cells were cardiac macrophages. By real-time polymerase chain reaction, the Y-chromosome-specific SRY DNA of MSCs from male donors was not detected in infarcted hearts of female recipients. Serial echocardiography studies at baseline and 4 weeks after cell transplantation showed that both unlabeled and labeled MSCs attenuated progressive left ventricular dilatation and dysfunction compared with controls. CONCLUSIONS - At 4 weeks after transplantation of SPIO-labeled MSCs, the transplanted cells are not present in the scar and the enhanced MRI signals arise from cardiac macrophages that engulfed the SPIO nanoparticles. However, both labeled and unlabeled cells attenuate left ventricular dilatation and dysfunction after myocardial infarction.
KW - Cells
KW - Magnetic resonance imaging
KW - Myocardial infarction
KW - Remodeling
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=34748907948&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.106.680231
DO - 10.1161/CIRCULATIONAHA.106.680231
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AN - SCOPUS:34748907948
SN - 0009-7322
VL - 116
SP - I38-I45
JO - Circulation
JF - Circulation
IS - 11 SUPPL. 1
ER -