Bone marrow mononuclear cell therapylimits myocardial infarct size through vascular endothelialgrowth factor

Abstract. No prior study has examined the effect of intravenousinjection of bone marrow mononuclear cells (MNCs) on myocardialinfarction size (IS). We tested the hypothesis thattransplantation of MNCs decreases IS through the release ofvascular endothelial growth factor (VEGF). Immediately afterligation of the left coronary artery of immunodeficient mice,PBS or MNCs were intravenously administered. Myocardial IS wassignificantly less in MNCs-treated mice than in PBS-treatedmice. Trace experiments showed accumulation of exogenouslyadministered MNCs into the vicinity of infarcted myocardium.Injection of MNCs did not affect capillary density afterinfarction, but did reduced myocardial cell apoptosis. Blockadeof VEGF by a neutralizing antibody or by gene transfer of asoluble form of Flt-1 VEGF receptor diminished the IS-limitingeffects of MNCs. In conclusion, injection of MNCs can reducemyocardial IS through the release of VEGF. The MNC therapy foracute myocardial infarction might improve prognosis of patientswith myocardial infarction.