Abstract 15311: Efficacy of Encapsulated GLP-1 Eluting Mesenchymal Stem Cells (CellBead): Results From a Blinded, Randomized, Dose-Finding Study in a Porcine Model of Acute Myocardial Infarction
Objective CellBeads are 170 μm alginate microspheres that contain mesenchymal stem cells (MSC) transfected to express glucagon-like peptide-1 (GLP-1), alongside the inherent paracrine factors. GLP-1 is a strong incretin hormone with anti-apoptotic and cardioprotective effects. We hypothesize that CellBeads delivered via intracoronary (IC) delivery promotes cardiomyocyte salvage, and ultimately abrogates adverse cardiac remodeling following AMI. A pilot study demonstrated that the IC approach is feasible and safe up to 60,000 CellBeads (∼ 5 million MSCs) without loss of coronary flow or induction of arrhythmias. The objective of this randomized controlled study was to evaluate the safety and efficacy of increasing doses of CellBeads on cardiac function in a porcine model of AMI (n=72).
Methods See figure
Results Fifty out of 72 animals survived infarct induction and the 8 week follow-up period, resulting in 7-9 animals in a total of six groups. There was no reduction of coronary flow reserve after infusion of all treatments. During the follow-up period there were no signs of ventricular arrhythmias on implanted event recorders. Although the study currently is still blinded, preliminary PV loop analysis shows an absolute increase in LVEF of 10.0 % between the best and poorest responding group (P= 0.045). Consistent with the LVEF, a decrease in end systolic volume of 40.7 mL (p=0.025) and end diastolic volume of 57.7 mL was observed (P=0.035). TUNEL staining showed a decrease of apoptotic cells in the border zone by 35% in the best responding group (P= 0.004). Additional immunohistochemical analysis is ongoing.
Conclusion CellBead therapy is a promising new platform to deliver stem cells and recombinant therapeutic proteins to the heart after AMI. In this dose-finding study, there is a clear benefit between groups, signalling a potential therapeutic effect. The fully-analyzed, unblinded data will be available by the time of Scientific Sessions 2011.
- © 2011 by American Heart Association, Inc.