1. INTRODUCTION 1.1. BACKGROUND AND RATIONALE OF THE STUDY The long term prognosis of patients suffering from acute myocardial infarction (AMI) has progressively improved since the introduction of reperfusion therapies and in particular primary angioplasty [1]. In the setting of ST-elevation myocardial infarction (STEMI), the immediate reopening of acutely occluded coronary arteries via primary angioplasty is the treatment of choice to salvage ischemic myocardium. However, the sudden re-initiation of blood flow can lead to a local acute inflammatory response with further endothelial and myocardial damage. This phenomenon, described as 'reperfusion injury', may explain why, despite optimum myocardial reperfusion, the short-term mortality after AMI approaches 7% [1] and the incidence of heart failure approaches 15-20% [2][3]. Despite the use of full conventional treatment, including ACE inhibitors, beta-blockers, aldosterone inhibitors and diuretics, in the context of randomised controlled trials yearly mortality rates of patients with post-infarction heart failure are still in the range of 10-13% and rehospitalisation for worsening of heart failure occurs at a yearly rate of 6-8 % [4]. Registry data indicate a more dismal outcome in real world clinical experience. A major reason for the high morbidity and mortality is that the heart has an inadequate regenerative response to the myocardial necrosis sustained following AMI; cell death from the ischemic damage can lead to progressive ventricular dilation and dysfunction through the processes of adverse left ventricular remodelling. However, the discovery of tissue resident cardiac stem cells in the mammalian heart [5] has challenged the long held belief that the heart is a terminally-differentiated organ and opens up the possibility of using bone marrow derived stem cells to repair the heart. Indeed, recent experimental studies documented that bone marrow-derived cell (BMC) injection into the infarcted heart stimulates the formation of newly formed cardiac myocytes, although the origin of these myocytes is still a matter of debate[6]. Numerous pre-clinical studies provided high degree of evidence that bone marrow derived cells do contribute to cardiac repair after acute myocardial injury, limit infarct expansion and improve cardiac function most likely via a paracrine mechanism of action. Pre-clinical evidence is corroborated by several small to intermediate size clinical trials demonstrating beneficial effects of bone marrow derived cells on top of the state-of-the-art reperfusion treatment [7]. For this reason, European Community has recently funded within FP-7 "The effect of intracoronary reinfusion of bone marrow derived mononuclear cells (BM-MNC) on all cause-mortality in acute myocardial infarction (BAMI)" project aimed to definitively demonstrate the efficacy of BM-MNC in patients with myocardial infarction.