Objective To investigate the potential ability of MRI in tracking magnetically labelled 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. Their autogeneic bone marrow-derived mesenchymal stem cells (MSCs) was cultured and doubly labled with ferumoxides and DAPI. At the 14th day after MI, labelled MSCs were injected intramyocardially into peri-infarct zone and normal myocardium. At the 14th day after MSCs transplantation, the size and location of the myocardial infarction were assessed by using delayed-enhancement MRI (DE-MRI). The contrast and the volume of the MR-MSCs hypointense lesion from the FGRE images were acquired. At 24 and 3 weeks after injection, 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.
Results At the 14th day after MSCs transplantation, DE-MRI showed the infarct in all animals and the mean infarction size was (33.60±9.80)% of the left ventricular area. At 24 h after injection, the contrast and the size of the lesions showed no statistical difference between in peri-infarct zone and in normal myocardium. At 3 weeks after injection, the contrast of the lesions in peri-infarct zone decreased rapidly than that in normal myocardium (26.88±7.27 vs 15.00±4.51, p=0.0003). Post mortem analysis showed that fluorescently labelled MSCs were demonstrated on histological sections. There were much more dense fluorescently labled MSCs per high power fields in injection sites of normal myocardium than in injection sites of peri-infarct zone (106±25/HPF vs 143±31/HPF, p=0.0293). At 3 weeks, there was less fibrosis in MSCs injection sites with more surviving myocardium. In MSCs injection sites of the peri-infarct zone, the capillary density was significantly more than that in control sites (13.40±4.00/HPF vs 9.40±3.10/HPF, p=0.0229).
Conclusions MRI of MSCs is feasible and represents a method for noninvasively tracking the quantity and location of intramyocardial delivery after MI. But to semi-quantitatively analyse the development of transplanted MSCs by MRI is not dependable.