Abstract 3127: Reparative Capacity of Mesenchymal Stem Cells is Impaired by Iron-Oxide Labeling after Extensive Myocardial Infarction
Background: Magnetic labeling of mesenchymal stem cells (MSCs) with superparamagnetic iron oxide (SPIO) could facilitate in-vivo targeting and tracking of transplanted MSCs for myocardial repair. We sought to determine whether the reparative capacity of MSCs is affected by iron-oxide labeling in a rat model of extensive myocardial infarction (MI).
Methods and Results: Rat MSCs were labeled with SPIO [Endorem(ferumoxides)]. Seven days after MI, rats were randomized to injections of either 2x106 SPIO-labeled MSCs, 2x106 unlabeled MSCs or saline (control), (n=5 each). Left ventricular (LV) remodeling and function (+SE) were assessed by serial echocardiography studies at baseline and four weeks after cell transplantation. In another group (n=2), MSCs were labeled with BrdU. SPIO-labeled cells were clearly visualized in the infarcted myocardium by serial MRI studies throughout the four-week study period. The presence of labeled cells was confirmed by iron and BrdU staining on postmortem specimens. Both unlabeled and SPIO-labeled MSCs attenuated LV dilatation and LV dysfunction, compared with controls. However, this beneficial effect was less remarkable in SPIO-labeled compared with unlabeled MSC treatment. Specifically, LV diastolic area increased by 27±5%, 47±2% vs. 75±8% in the unlabeled cells, labeled cells and controls, respectively (p<0.05 vs. control). LV systolic area increased by 31±3%, 50±5% vs. 142±29, respectively (p< 0.01 vs. control). LV fractional shortening decreased by 17±13%, 26±10% vs. 36±10% (p=0.49 and p=0.82 vs. control, respectively).
Conclusions: The present study suggests, for the first time, that iron labeling diminishes the reparative capacity of mesenchymal stem cells in rats with extensive MI. Our findings raise concern regarding the applicability of this cell tracking technique in future clinical trials of stem cell-based therapy.