Role of a paracrine action of mesenchymal stem cells in the improvement of left ventricular function after coronary artery occlusion in rats

摘要

Purpose: We aimed to determine whether soluble factors released by culturednmesenchymal stem cells (MSCs) improved cardiac function in an experimental model ofnmyocardial infarction. Methods: MSCs were cultured in fresh medium. The conditionednmedium, which contained factors secreted by MSCs, was collected after 4 days of culture.nFischer rats with 1-week-old myocardial infarction were divided into four groups thatnreceived: saline (n = 12); fresh medium (n = 10); conditioned medium (n = 8); or 2 millionnMSCs in fresh medium (n = 10) by direct intramyocardial injection. A total of 4 weeks later,nleft ventricular (LV) function was assessed by LV angiogram and by LV catheterization.nHearts were processed for histology. Results: Before treatment, LV angiogram assessmentndemonstrated that the baseline LV function was comparable among the four groups. Atn4 weeks after treatment, LV angiogram and LV catheterization showed that LV ejectionnfraction was better in the fresh medium (49.5 ± 1.0%), conditioned medium (48.5 ± 2.1%)nand MSCs groups (49.9 ± 4.2%) than in the saline group (43.7 ± 1.2%; p < 0.05). There werenno significant differences in heart rate, blood pressure, postmortem LV volume, infarct sizenor septum thickness among the groups. The scar thickness was similar in the salinen(395 ± 31 μm), fresh medium (404 ± 30 μm) and conditioned medium (397 ± 34 μm)ngroups, but significantly thicker in the MSCs group (560 ± 51 μm; p < 0.05). Conclusion:nFresh medium, conditioned medium and MSC injection all improved LV function at 4 weeksnafter treatment compared with saline treatment in a rat myocardial infarct model; onlynMSCs increased wall thickness. Since the culture medium contains nutrients and bovinenserum, the roles of the soluble factors released by MSCs might be masked. The effect ofnthese nutrients needs further investigation.