Abstract 15663: A Novel Strategy for Increasing Myocardial Retention of Stem Cells Delivered by Intracoronary Infusion in a Porcine Model of Acute Myocardial Infarction
Background The relatively low myocardial retention of intracoronary infused stem cells remains a limitation of stem cell therapy in patients with acute myocardial infarction (AMI). We are the first to evaluate the effect of ultrasound-mediated microbubble destruction to increase the local retention of stem cells in a pig model of AMI.
Methods A porcine model of AMI was created using balloon occlusion of the distal left anterior descending (LAD) coronary artery for 90 min. 8 pigs were divided into a control and treatment group of 4 pigs each. After 7 days, the control group received intracoronary infusion of 20 million autologous adipose derived regenerative cells (ADRCs) labeled with BioPAL, a europium-containing nontoxic colloidal lanthanide. The treatment group received intracoronary infusion of 20 million labeled ADRCs plus ultrasound-mediated microbubble destruction. Localized Microbubble destruction was performed prior to cell infusion using 2 ml of Definity as the contrast reagent and the destruction procedure lasted for 6 minutes in the heart using a regular transthoracic echocardiogram probe (MI 0.8-1.2). All animals were sacrificed 60 min after cell infusion and hearts were harvested for quantitative retention analysis by neutron activation of BioPAL.
Results No adverse events were associated with ultrasound-mediated microbubble destruction in myocardium. Within the infarcted area, an average of 3.8% of infused cells were recovered in the treatment animals compared to 0% in the control animals (P=0.047). In the non-infarcted area, the retention rate was similar in both groups (P=0.741) (Table).
Conclusions Ultrasound-mediated microbubble destruction increased myocardial retention of stem cells delivered by intracoronary infusion in a porcine model of AMI. Further study with a large sample size and the correlation between the increased retention rate with an improved therapeutic outcome is needed.
- © 2011 by American Heart Association, Inc.