Bone Marrow-Derived Stem Cell Transfer in Acute Myocardial Infarctions

Despite early coronary reperfusion, salvage of ischemic myocardium is incomplete and loss of viable myocardium initiates a process of adverse left ventricular (LV) remodeling1, compromising clinical outcome.

Experimental data have suggested that autologous bone marrow-derived or circulating progenitor cells may be beneficial for LV function recovery, but underlying mechanisms are unclear and prominent cardiomyocyte transdifferentiation has only been reported under selected experimental conditions. Early non-randomized clinical investigations indicate feasibility, safety and enhanced functional recovery after autologous human bone marrow-derived stem cell (BMSC) infusion into the infarct-related artery. More recently, a randomized open study demonstrated improvement of LV systolic function but not of LV remodeling following BMSC transfer.

In the absence of trials, in which the control group reproduces the exact conditions of the cell transfer group, including bone marrow aspiration and a placebo intracoronary injection, the true benefit of cell transfer cannot be fully appreciated.

We, therefore, designed a randomized, double-blind, and placebo-controlled exploratory study to investigate the effect of autologous BMSC transfer on LV functional and structural recovery after myocardial infarction. In view of the exploratory nature of the study and to detect potential mechanisms for the biological effect, we also assessed myocardial perfusion and oxidative metabolism using serial 1-[11C]acetate positron emission tomography (PET).

Inclusion criteria

• patients with acute myocardial infarction with cumulative ST-segment elevation >=6mm, successful epicardial reperfusion after PCI and significant LV dysfunction

Exclusion criteria

• patients presenting within 2 hours of symptom onset (no dilution of any treatment effect from aborted infarctions)
• patients with prior coronary artery bypass grafting, pulmonary edema, cardiogenic shock or significant co-morbidities