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

Abstract

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 2ϫ10 6 SPIO-labeled MSCs, 2ϫ10 6 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

Migration of Neurotrophic Factors-Secreting Mesenchymal Stem Cells Toward a Quinolinic Acid Lesion as Viewed by Magnetic Resonance Imaging

“…Previous studies showed that this could pose a problem and demonstrated up to 100% phagocytosis of the transplanted MSCs, injected into a myocardial infarct scar [52]. Moreover, a recent study has claimed that rat-derived MSCs cannot survive more than 14 days, even in a naïve rat brain [53].…”

Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair

“…The uptake of i.v. injected PS-presenting liposomes by cardiac macrophages was investigated in a rat model of acute MI (23). Forty-eight h after MI, the SD rats were injected through the femoral vein with 0.03 M of PS-presenting liposomes containing iron oxide (2 μg∕mL) (n ¼ 4) or saline as a control (n ¼ 4).…”

Value of MR contrast media in image-guided body interventions

“…These agents have no negative effects on cell viability, proliferation or differentiation [81,82] . The toxicity of iron oxide particles is less than free gadolinium because free iron particles released from dead iron MR contrast media can be introduced into the intracellular compartments by endocytosis, phagocytosis or magnetoelectroporation.…”