Abstract 15053: Directing Stem Cells to the Infarcted Heart Using StemBells™: Introducing a Novel Technique Using Targeted Microbubbles
The major problem of stem cell therapy for myocardial infarction is the lack of persistence and engraftment of sufficient stem cells at the site of injury. We designed a novel technique to overcome this problem by directing stem cells to the infarcted area using dual-targeted microbubbles (MB) and ultrasound (US). Adipose derived stem cells (ASC) were coupled to MB using an antibody against CD90. This stem cell-bubble complex was named StemBell™. StemBells™ were targeted to the infarcted area via a second antibody: anti-CD54 directed against ICAM-1. Low-intensity pulsed US (1 MHz, 100 kPa) was applied to exert acoustic radiation force on the StemBells™. In vitro we demonstrated that the procedure to form StemBells™, as well as exposure to US had no negative effect on cell viability or adherence capacity. In a rat model of myocardial infarction, we demonstrated that 3h after intravenous injection of 1 million DAPI-labeled StemBells™, 8-fold more stem cells were present specifically in the infarcted CD54+ area (p<0.01 vs ‘ASC alone’; n=6). Furthermore, we showed that 35 days after StemBell™ injection the infarcted area was significantly reduced by 52% (p<0.05 vs control; n=10). Interestingly, the number of stem cells in the infarcted area correlated with improved fractional shortening (r=0.75, p<0.001), as determined by echocardiography. In conclusion, we successfully demonstrated proof-of-principle of a novel stem cell delivery technique that increased the number of stem cells at targeted site resulting in improved cardiac function and reduced infarct size. Finally, this study demonstrated for the first time a correlation between the number of stem cells and the functional improvement of the heart.
- © 2013 by American Heart Association, Inc.