Stem cell therapy for the broken heart: mini-organ transplantation.
BACKGROUND
Myocardial infarction (MI) is characterized by irreversible loss of cardiomyocytes, resulting in impaired ventricular function. Stem cell therapy using autologous progenitor cells has emerged as a promising approach. Experimental studies have demonstrated that highly selected hematopoeitic stem cells, which are characterized by the presence of the surface markers CD34 and CD133, may contribute to repair of the acutely infarcted myocardium by inducing neovascularization, inhibiting apoptosis, and promoting cardiomyogenesis. We sought, to evaluate the intracoronary injection of CD133+ stem cells for cardiac repair in patients with dysfunctional myocardium after an acute MI.


METHODS
In this Canadian randomized, double-blind, placebo-controlled, Phase I-II study ("COMPARE-AMI"), we are evaluating the feasibility, safety, and efficacy of intracoronary injection of selected CD133+ stem cells for cardiac repair in patients with impaired cardiac function after successfully stented acute MI. Since November 2007, we have enrolled 14 patients in the study. Their mean age was 50.5 +/- 9.1 years, including 93% men. The culprit lesion was always on the left anterior descending artery (LAD). Their maximum troponin and CKMB levels were 8.4 +/- 6.1 microg/L and 322 +/- 225 U/L, respectively.


RESULTS
Compared with the baseline, we observed a significant 8.7% improvement in left ventricular ejection fraction at 4 months follow-up, namely, from 41.3 +/- 5.5% to 50.0 +/- 8.2% (n = 7; P = .008). There were no protocol-related complications. Our trial is designed to recruit 40 patients who are randomized 1:1 to receive CD133+ cells or placebo.


CONCLUSIONS
There is a need to seek out new therapeutics for the treatment of ischemic heart disease addressing the early loss of viable myocytes. Stem cell transplantation has shown early promise; this appraisal needs well-designed, controlled studies.
Cardiology Department, Hôtel-Dieu de Montréal, Centre Hospitalier de L'Université de Montréal, Québec H2W 1T8, Canada.
S
S
Mansour
D C
DC
Roy
B
B
Lemieux
C
C
Ouellet
L-M
LM
Stevens
N
N
Noiseux
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology; D009202:Cardiomyopathies / Q000601:surgery*; D002637:Chest Pain / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006023:Glycoproteins / Q000032:analysis / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000601:surgery*; D018919:Neovascularization, Physiologic / Q000502:physiology; D010455:Peptides / Q000032:analysis / Q000276:immunology; D012449:Safety; D014182:Transplantation, Autologous
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides