© 2008 European Society of Cardiology
Human angiogenic cell precursors restore function in the infarcted rat heart: A comparison of cell delivery routes
a Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital and University of Toronto Toronto, Ontario, Canada
b TheraVitae Ltd Ness Ziona, Israel
* Corresponding author. MaRS Centre, Toronto Medical Discovery Tower, 3-702, 101 College Street, Toronto, Ontario, Canada M5G 1L7. Tel.: +1 416 581 7492; fax: +1 416 581 7493 E-mail address: renkeli{at}uhnres.utoronto.ca
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Abstract |
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Background: We recently isolated angiogenic cell precursors (ACPs) from human blood, which can induce angiogenesis in vitro.
Aims: In the present study, we used a nude rat model of ischaemic cardiomyopathy to compare the efficacy of intramyocardial and intracoronary ACP implantation, and to evaluate effects on cardiac function, scar size and angiogenesis.
Methods and results: Adult nude rats underwent coronary artery ligation. Six days later, ACPs (characterized in vitro prior to implantation) or culture media were injected directly into the ischaemic myocardial region or into the coronary artery via the aorta. Cardiac function was measured by echocardiography prior to and at 2 and 4 weeks after implantation. Scar morphology, cell engraftment, and myocardial angiogenesis were evaluated at 4 weeks. Two and four weeks after implantation, cardiac function declined in both of the control groups but improved in both the intramyocardial and intracoronary ACP groups. Significant reductions in myocardial scar area were only observed in the intramyocardial ACP group, while increases in blood vessel density, which were observed in all ACP recipients, were greatest in the intracoronary ACP group.
Conclusions: Human ACPs, delivered via intramyocardial or intracoronary injection, engrafted into damaged cardiac tissue and improved cardiac function within 4 weeks through effects on scar morphology and blood vessel formation.
Key Words: Cell transplantation • Angiogenic cell precursors • Myocardial ischaemia • Heart failure • Angiogenesis
Received January 21, 2008; Revised March 10, 2008; Accepted April 9, 2008
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