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(Circulation. 2007;116:I-38 – I-45.)
© 2007 American Heart Association, Inc.

Cell Transplantation and Tissue Regeneration

Iron-Oxide Labeling and Outcome of Transplanted Mesenchymal Stem Cells in the Infarcted Myocardium

Yoram Amsalem, MD; Yael Mardor, PhD; Micha S. Feinberg, MD; Natalie Landa, BSc; Liron Miller, MSc; Dianne Daniels, MSc; Aharon Ocherashvilli, PhD; Radka Holbova; Orna Yosef, PhD; Israel M. Barbash, MD; Jonathan Leor, MD

From the Neufeld Cardiac Research Institute (Y.A., M.S.F., N.L., L.M., R.H., O.Y., I.M.B., J.L.) and The Advanced Technology Center (Y.M., D.D., A.O.), Tel-Aviv University, Sheba Medical Center, Tel-Hashomer, Israel.

Correspondence to Jonathan Leor, MD, FACC, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel. E-mail leorj{at}post.tau.ac.il

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 2x10⁶ SPIO-labeled MSCs, 2x10⁶ 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.

Key Words: cells • magnetic resonance imaging • myocardial infarction • remodeling • transplantation

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