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

Purpose: We aimed to determine whether soluble factors released by cultured mesenchymal stem cells (MSCs) improved cardiac function in an experimental model of myocardial infarction. Methods: MSCs were cultured in fresh medium. The conditioned medium, which contained factors secreted by MSCs, was collected after 4 days of culture. Fischer rats with 1-week-old myocardial infarction were divided into four groups that received: saline (n = 12); fresh medium (n = 10); conditioned medium (n = 8); or 2 million MSCs in fresh medium (n = 10) by direct intramyocardial injection. A total of 4 weeks later, left ventricular (LV) function was assessed by LV angiogram and by LV catheterization. Hearts were processed for histology. Results: Before treatment, LV angiogram assessment demonstrated that the baseline LV function was comparable among the four groups. At 4 weeks after treatment, LV angiogram and LV catheterization showed that LV ejection fraction was better in the fresh medium (49.5 +/- 1.0%), conditioned medium (48.5 +/- 2.1%) and MSCs groups (49.9 +/- 4.2%) than in the saline group (43.7 +/- 1.2%; p < 0.05). There were no significant differences in heart rate, blood pressure, postmortem LV volume, infarct size or septum thickness among the groups. The scar thickness was similar in the saline (395 +/- 31 mu m), fresh medium (404 +/- 30 mu m) and conditioned medium (397 +/- 34 mu m) groups, but significantly thicker in the MSCs group (560 +/- 51 mu m; p < 0.05). Conclusion: Fresh medium, conditioned medium and MSC injection all improved LV function at 4 weeks after treatment compared with saline treatment in a rat myocardial infarct model; only MSCs increased wall thickness. Since the culture medium contains nutrients and bovine serum, the roles of the soluble factors released by MSCs might be masked. The effect of these nutrients needs further investigation.