In vivo contrast enhanced MRI for quantification of cardiac function and infarct size after stem cell therapies in mice

Introduction Local ischemia in the heart during myocardial infarction will result in massive cell death of rhythmically contracting cardiomyocytes. Unfortunately, regeneration of cardiomyocytes is rare and during left ventricular (LV) remodeling affected tissue is replaced by non-contractile fibrotic tissue. Stem cell-based therapies can either provide the heart with new functional cardiomyocytes or exert paracrine effects, thereby positively affecting LV remodeling [1]. In this study, the global effects of skeletal myoblast (SM) and mesenchymal stem cell (MSC) transplantation on infarcted mouse hearts were determined noninvasively with in vivo contrast enhanced cardiac MRI. Both cell types were isolated from Swiss mice to enable a direct comparison. Methods Myocardial infarction was induced in male Swiss mice by either cryoinjury or permanent occlusion (ligation) of the left coronary artery, immediately followed by injection of PBS (sham) or 2·10 GFP-positive SM or MSC in the centre of the infarction [2]. Cells were isolated from 17.5d embryos and adult mice respectively. Non-operated Swiss mice served as controls. Each group consisted of 1-4 mice. After 14 days, longand short-axis ECG and respiratory triggered CINE FLASH images (TE/TR/α/NEX/FOV/matrix = 1.8ms/7ms/15/6/3x3cm/ 192x192) were acquired at 9.4T to determine LV global functional parameters. Infarct size was assessed on T1w short-axis multislice FLASH images (TR/α/slice thickness = 63ms/60/1mm) acquired before and up to 30min after the injection of 0.3mmol Gd-DTPA/kg. Data analysis was performed with CAAS-MRV FARM software (Pie Medical Imaging). Results Two weeks after the induction of myocardial infarction, infarct size was reduced by transplantation of either SM and MSC in both cryoinjured and permanently occluded hearts (figures 1&2). Ejection fractions (EF), end-diastolic and -systolic volumes (EDV and ESV, respectively) were improved in all treatment groups, except for mice with cryoinjury transplanted with SM. However, all functional parameters were still impaired compared to control mice. End-diastolic mass was decreased by ~17% in mice with permanent occlusion transplanted with SM or MSC, whereas only a minor decrease was found in mice with cryoinjury (not shown). Therapy was most effective in mice with permanent occlusion, where relative infarct size was decreased by 13.8% and 34.5% after transplantation of SM and MSC respectively. This was accompanied by an increase in EF of 24.8% and 63.6%, achieved by a reduction in EDV and ESV of 30-40%.