Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging.
BACKGROUND
Experimental and initial clinical studies suggest that transplantation of circulating blood- (CPC) or bone marrow-derived (BMC) progenitor cells may beneficially affect postinfarction remodeling processes after acute myocardial infarction (AMI). To relate functional characteristics of the infused cells to quantitative measures of outcome at 4-month follow-up, we performed serial contrast-enhanced MRI and assessed the migratory capacity of the transplanted progenitor cells immediately before intracoronary infusion.


RESULTS
In 28 patients with reperfused AMI receiving either BMCs or CPCs into the infarct artery 4.7+/-1.7 days after AMI, serial contrast-enhanced MRI performed initially and after 4 months revealed a significant increase in global ejection fraction (from 44+/-10% to 49+/-10%; P=0.003), a decrease in end-systolic volume (from 69+/-26 to 60+/-28 mL; P=0.003), and unchanged end-diastolic volumes (122+/-34 versus 117+/-37 mL; P=NS). Infarct size, measured as late enhancement (LE) volume, decreased significantly, from 46+/-32 to 37+/-28 mL (P<0.05). There was a significant correlation between the reduction in LE volume and global ejection fraction improvement. The migratory capacity of transplanted cells as assessed ex vivo toward a gradient of vascular endothelial growth factor for CPCs and stromal cell derived factor-1 for BMCs was closely correlated with the reduction of LE volume. By multivariate analysis, migratory capacity remained the most important independent predictor of infarct remodeling.


CONCLUSIONS
Analysis of serial contrast-enhanced MRI suggests that intracoronary infusion of adult progenitor cells in patients with AMI beneficially affects postinfarction remodeling processes. The migratory capacity of the infused cells is a major determinant of infarct remodeling, disclosing a causal effect of progenitor cell therapy on regeneration enhancement.
Britten
M B
MB
Department of Cardiology, J.W. Goethe-University Frankfurt, Frankfurt, Germany.
Abolmaali
N D
ND
Assmus
B
B
Lehmann
R
R
Honold
J
J
Schmitt
J
J
Vogl
T J
TJ
Martin
H
H
Schächinger
V
V
Dimmeler
S
S
Zeiher
A M
AM
D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D017023:Coronary Angiography; D003331:Coronary Vessels; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007089:Image Enhancement; D007261:Infusions, Intra-Arterial; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy*; D015425:Myocardial Reperfusion; D020127:Recovery of Function; D033581:Stem Cell Transplantation / Q000379:methods*; D015607:Stents; D013318:Stroke Volume; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D042461:Vascular Endothelial Growth Factor A