Xiuyu Chen, Presenter: Nothing to Disclose

Shihua Zhao, Abstract Co-Author: Nothing to Disclose

Our aim was to in vivo monitoring the magnetically labeled mesenchymal stem cells (MSCs) after transplantation into infarcted rat hearts and determining the effect on cardiac function using a 7.0 T magnetic resonance imaging (MRI) scanner.

Rat MSCs (male) were dual-labeled with fluorescent micron-sized particles of iron oxide (MPIO) and DM-DiI. Seven days after MI, rats (females) were randomized to injections of labeled MSCs (2×106 cells/50μL) or saline (50μL) into the border zone of infarcted myocardium. MRI was used to evaluate stem cell migration, signal intensity changes and cardiac function at baseline (1 day before transplantation), 3 days, 2 weeks and 4 weeks after transplantation, respectively. At each time point after transplantation, myocardial tissue from 5~8 hearts was analyzed by postmortem analyses.

MSCs could be efficiently and safely labeled with MPIO, and multipotentiality was not affected. MR hypointensities caused by the MPIOs were detected on T2*-weighted imaging at all times after MSCs transplantation. As time progressed, the signal gradually weakened and the area shrank. By real-time polymerase chain reaction with Y-chromosome specific primers, the number of grafted MSCs in the heart decreased rapidly from 11.5% (3 days) to ~0.1% (4 weeks). At 4 weeks, double staining for iron and CD68 (resident macrophage marker) showed that most of the iron-positive cells were cardiac macrophages. This was further confirmed by transmission electron microscopy. At baseline, cardiac function measured by cine-MRI was similar between groups. By 4 weeks, ejection fractions in control hearts had significantly decreased, but this was not evident in MSC-treated hearts. In addition, MSC-treated rat hearts had significantly increased capillary density in the peri-infarct region, and lower cardiomyocytes apoptosis and collagen deposition.

The survival of transplanted MPIO-labeled MSCs is poor at 4 weeks after transplantation, and the MR hypointensities mainly arise from cardiac macrophage that engulfed the MPIO particles. However, MSCs attenuate left ventricular dilatation and dysfunction after MI, which may attribute to enhanced angiogenesis, inhibition of host cell apoptosis and fibrosis.

our results indicate that iron oxide are not reliable marker for tracking the transplanted stem cells.

Chen, X, Zhao, S, Mesenchymal Stem Cells Improve Cardiac Function after Myocardial Infarction in Rats without Long-term Survival: A Serial 7.0T MRI Study.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14004773.html