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Updated: May 3, 2026
Construction of Defined Human Engineered Cardiac Tissues to Study Mechanisms of Cardiac Cell Therapy
Published on: March 1, 2016
Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium
Volker Schächinger1, Alexandra Aicher, Natascha Döbert
1Department of Medicine III, Division of Cardiology, JW Goethe University Frankfurt, Frankfurt am Main, Germany.
Insights
Proangiogenic progenitor cells administered via intracoronary infusion home to damaged heart tissue in myocardial infarction patients. Cell retention decreases over time, with greater homing observed in acute infarcts with low viability and reduced coronary flow reserve.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Cell Therapy
Background:
- Intracoronary infusion of progenitor cells shows promise for improving myocardial function in ischemic heart disease.
- The homing patterns and determinants of proangiogenic progenitor cell engraftment in damaged myocardium remain unclear.
Purpose of the Study:
- To investigate the extent and predictors of proangiogenic progenitor cell homing to the myocardium after intracoronary infusion.
- To understand the mechanisms underlying progenitor cell engraftment in patients with myocardial infarction.
Main Methods:
- Proangiogenic progenitor cells were isolated, cultured, and labeled with radioactive indium oxine ((111)In-oxine).
- Radiolabeled cells were infused into patients with prior myocardial infarction.
- Myocardial viability and microcirculatory function were assessed using (18)F-fluorodeoxyglucose-positron emission tomography and intracoronary Doppler measurements, respectively.
Main Results:
- A significant amount of radioactivity (mean 6.9%) was detected in the heart one hour post-infusion, decreasing to 2% by 3-4 days.
- Cell homing was highest in acute myocardial infarction (<14 days) and progressively decreased in later stages.
- Low myocardial viability and reduced coronary flow reserve were identified as significant predictors of progenitor cell homing (P<0.05).
Conclusions:
- Intracoronary infusion of (111)In-oxine-labeled progenitor cells results in substantial cardiac retention, confirming myocardial homing.
- The retention of progenitor cells in the heart diminishes over time post-myocardial infarction.
- Proangiogenic progenitor cells preferentially target acutely infarcted myocardium with low viability and impaired coronary flow reserve.
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 ((111)In-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 (18)F-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 (
Conclusions:
In patients after myocardial infarction undergoing intracoronary infusion of (111)In-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.
