Cell therapy—success does not come easy

M Tendera, W Wojakowski - European heart journal, 2009 - academic.oup.com
M Tendera, W Wojakowski
European heart journal, 2009academic.oup.com
More than 6 years ago the initial report on clinical application of bone marrow-derived
mononuclear cells (BMMNCs) in patients with acute myocardial infarction (AMI) opened up a
new era of regenerative cardiology and brought with it great enthusiasm and expectations. 1
Since then, numerous clinical trials have been carried out with the aim of assessing the
efficacy and safety of stem cell therapy. In all cases the safety of the therapy was proved, but
its effectiveness still remains a matter of controversy and fierce debate. 2 Since stem cell …
More than 6 years ago the initial report on clinical application of bone marrow-derived mononuclear cells (BMMNCs) in patients with acute myocardial infarction (AMI) opened up a new era of regenerative cardiology and brought with it great enthusiasm and expectations. 1 Since then, numerous clinical trials have been carried out with the aim of assessing the efficacy and safety of stem cell therapy. In all cases the safety of the therapy was proved, but its effectiveness still remains a matter of controversy and fierce debate. 2 Since stem cell therapy trials in patients with AMI began, the primary outcome measure has been the change in left ventricular (LV) ejection fraction (EF). The LV volumes have also been analysed to assess more accurately the cause of the changes in LVEF after bone marrow cell (BMC) therapy. 1, 3–6 So far, the data on the effectiveness of BMC infusion in improving the global LV contractility remain equivocal.
For example, the ASTAMI trial showed no improvement of LVEF and no reduction of end-diastolic volume in patients treated with intracoronary transfer of BMCs. In this trial, a significant improvement of LVEF was observed not only in patients treated with BMCs, but also in the control group. 7 The BOOST trial showed an initial improvement in LVEF 6 months after BMC infusion, but the difference between the BMC arm and the control group was no longer significant at 18 months. 8 On the other hand, REPAIR-AMI, so far the largest randomized placebo-controlled study, showed a significant improvement in LVEF at 4 months follow-up by 2.5% in patients receiving BMCs. The increase in LVEF co-existed with an improvement of regional contractility including the segments located in the area of infarction. 3 It has been hypothesized that these inconsistencies can be due to differences in trial designs, including time from reperfusion to BMC transfer, the type and number of infused cells, and the method of cell isolation. 9 It seems that cell therapy has more favourable effects when initiated later—at least 4 days after reperfusion. 3 However, in some studies which showed no significant
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