Background: Engraftment and survival of stem cells in the infarcted myocardium remain problematic in cell-based therapy for cardiovascular disease. To overcome these issues, encapsulated mesenchymal stem cells (eMSCs) were developed that were transfected to produce glucagon-like peptide-1, an incretin hormone with known cardioprotective effects, alongside MSC endogenous paracrine factors. This study was designed to investigate the efficacy of different doses of intracoronary infusion of eMSC in a porcine model of acute myocardial infarction (AMI). Methods and Results: One hundred pigs were subjected to a moderate AMI (posterolateral AMI; n=50) or a severe AMI (anterior AMI; n=50), whereupon surviving animals (n=36 moderate, n=33 severe) were randomized to receive eitherintracoronary infusion of 3 incremental doses of eMSC or Ringers' lactate control. Cardiac function was assessed using invasive hemodynamics, echocardiography, and histological analysis. A trend was observed in the moderate AMI model, whereas in the severe AMI model, left ventricular ejection fraction improved by +9.3% (P=0.004) in the best responding eMSC group, because of a preservation of left ventricular end-systolic volume. Arteriolar density increased 3-fold in the infarct area (8.4±0.9/mm<inf>2</inf> in controls versus 22.2±2.6/mm<inf>2</inf> in eMSC group; P<0.001). Although not statistically significant, capillary density was 30% higher in the border zone (908.1±99.7/mm<inf>2</inf> in control versus 1209.0±64.6/mm<inf>2</inf> in eMSC group; P=ns).. Conclusions-eMSCs enable sustained local delivery of cardioprotective proteins to the heart, thereby enhancing angiogenesis and preserving contractile function in an animal AMI model..

Acute anterior wall myocardial infarction, Acute myocardial infarction, Cell therapy, Glucagon-like peptide-1, Mesenchymal stromal cells, Percutaneous coronary intervention,
Circulation. Cardiovascular Interventions
Department of Cardiology

Jong, R, van Hout, G.P.J, Houtgraaf, H.J, Kazemi, K, Wallrapp, C, Lewis, A.L, … Duckers, H.J. (2014). Intracoronary infusion of encapsulated glucagon-like peptide-1-eluting mesenchymal stem cells preserves left ventricular function in a porcine model of acute myocardial infarction. Circulation. Cardiovascular Interventions, 7(5), 673–683. doi:10.1161/CIRCINTERVENTIONS.114.001580