Autologous bone marrow mononuclear stem cells for acute myocardial infarction: is it only about time?

In 2002, Strauer et al. reported the results of the first phase I study testing the safety of intracoronary (IC) administration of autologous bone marrow mononuclear stem cells (BMMSCs) for acute myocardial infarction (AMI). Since then, we have seen a series of trials using mixed cell types with heterogeneous designs in terms of both the number and the timing of BMMSCs administration that have yielded conflicting results (Figure 1). For example, Nowbar et al. found no beneficial effect on left ventricular ejection fraction (LVEF) when analysing BMMSCs trials without any discrepancies, while a metaanalysis by Afzal et al. (48 studies; 2602 patients) showed an improvement in both LVEF (+2.92%) and infarct size (22.25%), as well as remodelling. Taken as a whole, these contradictory findings have left the general cardiology community somewhat indifferent and have arguably shrouded the field of BMMSC AMI research in a dark fog from which it has yet to emerge. In this issue of the journal, Choudry et al. present the results of the REGENERATE-AMI trial, evaluating the effect of IC autologous BMMSCs on left ventricular (LV) function when delivered within 24 h of successful reperfusion therapy. While REGENERATE-AMI did not meet its primary endpoint, there is much potential value in trying to place this trial’s design and results in context in order hopefully to illuminate a way forward for regenerative therapy after successfully perfused AMI. REGENERATE-AMI enrolled 100 patients with AMI across five European centres from 2008 to 2013, who were randomized to either IC BMMSCs or placebo within 24 h of successful percutaneous coronary intervention (PCI). The primary endpoint was the change in the LVEF at 1 year using advanced cardiac imaging. Secondary endpoints included infarct size and LV remodelling at 3, 6, and 12 months. In addition, biological and clinical heart failure (HF) parameters, quality of life scores, and 1-year major adverse cardiac event (MACE) rates were analysed. Similar to several previous trials, the authors found that injection of BMMSCs resulted in a reduction in infarct size, but without any improvement in LVEF, New York Heart Association (NYHA) class, N-terminal pro brain nariuretic peptide (NT-proBNP) levels, or the MACE rate. The trial did confirm, however, that ‘early’ BMMSCs injection was both feasible and safe.