Dynamic MRI of ferumoxide-labeled bone mesenchymal stem cells after transplantation in infarcted myocardium

Objective To investigate the ability of magnetic resonance imaging (MRI) in tracking magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model.Methods Adult Chinese mini-pigs (n = 6) were subjected to open-chest experimental MI operation.Their antegeneic bone marrow-derived mesenchymal stem cells ( MSCs ) was cultured and doubly labeled with ferumoxides and DAPL On the 14 th day after MSCs transplantation, the size and location of the myocardial infarction were assessed by using delayed-enhancement MRI (DE-MRI). Then the labeled MSCs were injected intramyocardially into peri-infarct zone and normal myocardium. At 24 hrs and 3 weeks after injection, the contrast and the volume of the MR-MSCs hypointense lesion from the MR images were acquired, and the contrast was determined using the difference in signal intensity between the hypointense and normal myocardium divided by signal intensity of the normal region.After humane euthanasia, the heart was excised and histology corresponding to MRI slices that demonstrated MR-MSCs lesions was performed.Repeated-measures ANOVA and a paired t test were used for comparison of the contrast and the volume of the MR-MSCs hypointense lesion at different time points. Comparisons between independent groups were performed with the standard Student t test.Results The labeling efficiency of ferumoxides and DAPI was 100% . On the 14 th day after the MI operation, the average percentage of infracted myocardial area was (33.6±8.9)% .Twenty- four hours after MSCs transplantation, MSCs injection sites appeared as ovoid hypointensive lesions with sharp border on T2 * images. At 24 h after injection, the signal contrast [(67.00±5.48)% vs (61.92 ±7.76)%,t = 1.65,P =0.1158] and the size [(0.56 ±0.24) cm2 vs (0.52 ± 0.25 ) cm2, t = 0.39, P = 0.7044 ] of the lesions showed no statistical difference between the peri infarct zone and the normal myocardium.At 3 weeks after injection, the signal contrast decreased and the size diminished both in the peri-infarct zone and in the normal myocardium. Moreover, the contrast of the lesions in peri-infarct zone decreased more significantly than that in normal myocardium [(26.88 +7.27)%vs (15.00 :t:4.51)%, F =20.08, P =0.0003].Post mortem analysis found the fluorescontly labeled MSCs demonstrated on histological sections.There were much more dense fluorescently labled MSCs per high power fields at injection sites of normal myocardium than at injection sites of peri-infarct zone [ (106 ±25 )/HPF vs ( 143 ± 31 )/HPF, t = - 2.47, P = 0.0293 ].In MSCs injection sites of the peri-infarct zone,the capillary density was significantly higher than that in control sites [ (13.4 ± 4.0 )/HPF vs (9.4 ±3.1 )/HPF, t = 2.49, P = 0.0229].At 3 weeks after injection, ferumoxide was contained within partial original MSCs.Conclusion Magnetic resonance imaging of MSCs is a feasible method for the in vivo tracking of transplanted stem cells and could reflect the tendency of the local stem cell quantity, but there still has limitation for the semi-quantitation of the transplanted stem cells. Key words: Magnetic resonance imaging; Mesenchymal stem cell; Myocardial infarction