Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction.
BACKGROUND
Administration of cardiac progenitor cells (CPCs) 4 hours after reperfusion ameliorates left ventricular function in rats with acute myocardial infarction (MI). Clinically, however, this approach is not feasible, because expansion of autologous CPCs after acute MI requires several weeks. Therefore, we sought to determine whether CPCs are beneficial in the more clinically relevant setting of an old MI (scar).


RESULTS
One month after coronary occlusion/reperfusion, rats received an intracoronary infusion of vehicle or enhanced green fluorescent protein-labeled CPCs. Thirty-five days later, CPC-treated rats exhibited more viable myocardium in the risk region, less fibrosis in the noninfarcted region, and improved left ventricular function. Cells that stained positive for enhanced green fluorescent protein that expressed cardiomyocyte, endothelial, and vascular smooth muscle cell markers were observed only in 7 of 17 treated rats and occupied only 2.6% and 1.1% of the risk and noninfarcted regions, respectively. Transplantation of CPCs was associated with increased proliferation and expression of cardiac proteins by endogenous CPCs.


CONCLUSIONS
Intracoronary administration of CPCs in the setting of an old MI produces beneficial structural and functional effects. Although exogenous CPCs can differentiate into new cardiac cells, this mechanism is not sufficient to explain the benefits, which suggests paracrine effects; among these, the present data identify activation of endogenous CPCs. This is the first report that CPCs are beneficial in the setting of an old MI when given by intracoronary infusion, the most widely applicable therapeutic approach in patients. Furthermore, this is the first evidence that exogenous CPC administration activates endogenous CPCs. These results open the door to new therapeutic applications for the use of autologous CPCs in patients with old MI and chronic ischemic cardiomyopathy.
Tang
Xian-Liang
XL
Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292, USA.
Rokosh
Gregg
G
Sanganalmath
Santosh K
SK
Yuan
Fangping
F
Sato
Hiroshi
H
Mu
Jianyao
J
Dai
Shujing
S
Li
Chengxin
C
Chen
Ning
N
Peng
Yong
Y
Dawn
Buddhadeb
B
Hunt
Greg
G
Leri
Annarosa
A
Kajstura
Jan
J
Tiwari
Sumit
S
Shirk
Gregg
G
Anversa
Piero
P
Bolli
Roberto
R
D000818:Animals; D049109:Cell Proliferation; D003331:Coronary Vessels; D005355:Fibrosis; D049452:Green Fluorescent Proteins; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000166:cytology; D019899:Paracrine Communication; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000628:therapy*
D049452:Green Fluorescent Proteins