T-cell receptor repertoire diversity improves after intramyocardial injection of bone marrow cells in patients with severe coronary artery disease

Abstract

Background: Mast cells are multifunctional cells containing various mediators, such as cytokines, proteases, and histamine. Recent studies have shown that mast cells can affect disease progression after acute myocardial infarction. Here, we evaluated the effects of mast cell granules (MCGs) at different concentrations on various cell types, such as rat neonatal cardiomyocytes (rCMs), human endothelial progenitor cells (hEPCs), and human umbilical vein endothelial cells (hUVECs), and in a rat model of myocardial infarction. Methods and Results: In the in vitro assay, we treated rCMs, hEPCs, and hUVECs with MCGs [1%, 0.1%, 0.01%, and 0.001% of the original dose (2×105 cells/ml)] for 4 or 24 h. In the in vivo assay, we injected MCGs (2 or 20 μl) into an infarcted rat heart. We analyzed cell survival, cell signals, angiogenesis, and preservation of left ventricular function. MCGs increased capillary tube formation and migration in hEPCs and hUVECs, and phosphorylation of Akt and ERK in rCMs. In the rat model, both 2 and 20 μl MCGs increased capillary density in the infarct area to three times that in the control rats (Pb.05 in each). Left ventricular function improved in the group treated with 2 μl MCGs (Pb.05). Conclusions: MCGs play a role in the regulation of angiogenesis and cell survival and may result in improved left ventricular function after myocardial infarction.