Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium

Background - Clinical trials indicate a beneficial effect of intracoronary infusion of progenitor cells on myocardial function in patients with ischemic heart disease. The extent and potential determinants of proangiogenic progenitor cell homing into the damaged myocardium after intracoronary infusion and the underlying mechanisms are still unknown. Method and Results - Circulating proangiogenic progenitor cells isolated from peripheral blood and cultivated for 3 days were labeled with radioactive indium oxine ( In-111-oxine). Radiolabeled proangiogenic progenitor cells (7.6 +/- 3.0 MBq, mean +/- SD) were administered to patients with previous myocardial infarction and a revascularized infarct vessel at various stages after infarction (5 days to 17 years). Viability of the infarcted myocardium was determined by F-18-fluorodeoxyglucose-positron emission tomography and microcirculatory function by intracoronary Doppler measurements. One hour after application of progenitor cells, a mean of 6.9 +/- 4.7% (range, 1% to 19%; n = 17) of total radioactivity was detected in the heart, which declined to 2 +/- 1% after 3 to 4 days. Average activity within the first 24 hours was highest among patients with acute myocardial infarction (<= 14 days; 6.3 +/- 2.9%; n = 8) and progressively decreased in patients treated in an intermediate phase (> 14 days to 1 year; 4.5 +/- 3.2%; n = 4) or a chronic stage (infarct age >1 year; 2.5 +/- 1.6%; n = 5). Low viability of the infarcted myocardium and reduced coronary flow reserve were significant (P <0.05) predictors of proangiogenic progenitor cell homing. Conclusions - In patients after myocardial infarction undergoing intracoronary infusion of In-111-oxine-labeled proangiogenic progenitor cells, a substantial amount of radioactivity is detected for several days in the heart, indicating homing of progenitor cells to the myocardium. The amount of proangiogenic progenitor cells retained in the heart decreased progressively with time after the acute myocardial infarction. Proangiogenic progenitor cells preferentially home to extensive acute myocardial infarcts characterized by low viability and reduced coronary flow reserve.