title: Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction.
abstract: 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.
authors.affiliation: Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Xian-Liang
authors.initials: XL
authors.lastname: Tang
authors.forename: Gregg
authors.initials: G
authors.lastname: Rokosh
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Sanganalmath
authors.forename: Fangping
authors.initials: F
authors.lastname: Yuan
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Jianyao
authors.initials: J
authors.lastname: Mu
authors.forename: Shujing
authors.initials: S
authors.lastname: Dai
authors.forename: Chengxin
authors.initials: C
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Peng
authors.forename: Buddhadeb
authors.initials: B
authors.lastname: Dawn
authors.forename: Greg
authors.initials: G
authors.lastname: Hunt
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.forename: Jan
authors.initials: J
authors.lastname: Kajstura
authors.forename: Sumit
authors.initials: S
authors.lastname: Tiwari
authors.forename: Gregg
authors.initials: G
authors.lastname: Shirk
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
mesh_terms: 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*
chemical_list: D049452:Green Fluorescent Proteins