Improving myocardial viability: clinical implications for the use of bone marrow-derived stem cell infusion after acute myocardial infarction

The treatment of acute myocardial infarction (AMI) has evolved substantially over the past three decades, after an improvement in the mortality rate of AMI due to thrombolytics [1,2] and primary percu taneous intervention for coronary reperfusion [3]. Less than a decade ago, initial reports on the clinical application of mono nucleated bone marrow-derived stem cells (BMCs) in patients with AMI opened up a new era of regenerative cardiology and brought with it great enthusiasm [4]. Since then, numerous clinical trials have been carried out, with the aim of assessing the efficacy and safety of bone marrow stem cell therapy. Randomized Phase II trials have demonstrated contradictory results, but finally a significant improvement in cardiac function assessed by left ventricular ejection fraction (LVEF) after cell therapy was highlighted in meta-analyses [5–7]. Some of the discrepancies between some trials may be explained by differences in cell isolation and storage procedures [8]. Nevertheless, there was some evidence to suggest that BMC-based therapy is effective at improving LVEF in certain subpopulations, such as patients with large AMI and decreased LVEF [7,9]. Improvement of LVEF is of clinical relevance, since an increased LVEF achieved with cell transplantation is within an intriguingly similar range compared with established therapeutic strategies [10]. Several mechanisms of action have been suggested, but improvement in myocardial viability had never been assessed before the Bone Marrow in Acute Myocardial Infarction (BONAMI) trial [11].