Abstract 12043: Intracoronary Infusion of Encapsulated, GLP-1 Eluting Human Mesenchymal Stem Cells (Cellbeads) Improves Mesenchymal Stem Cell Retention, Preserves Myocardial Function and Enhances Local Angiogenesis in a Porcine Model of Moderate and Severe Acute Myocardial Infarction
Background: Retention of stem cells in the infarcted myocardium remains a problem for cell-based therapy for cardiac repair. CellBeadsTM are 170 μm alginate microspheres that encapsulate clusters of human mesenchymal stem cells (MSC), and were developed to improve MSC survival and myocardial retention following intracoronary infusion. The MSC were transfected to stably express recombinant glucagon-like peptide-1 (GLP-1), a potent incretin hormone with anti-apoptotic and cardioprotective properties, alongside the paracrine factors of the MSC.
Methods and Results: We performed a double-blinded, dose-finding study of intracoronary (IC) delivered CellBeads in two porcine AMI models. An intermediate size myocardial infarct was induced by a 90 min balloon occlusion of the LCx in 50 Landrace pigs. In addition, a large AMI was induced by 90 min ligation of the LAD in another 50 Landrace pigs. Surviving animals (n=36 LCx, n=37 LAD,) were randomized to receive IC infusion of 3 incremental doses of CellBeads or Ringers’ Lactate control. Cardiac function was assessed using invasive hemodynamics and echocardiography. Histological analysis was performed at 8 week follow-up.
The beneficial effects of CellBeads therapy were more pronounced in the severe LAD AMI model. In animals that have been treated with 20.000 GLP1-CellBeads, global left ventricular ejection fraction (LVEF) improved by 9.3% (p≤0.001) at 8 week follow-up as compared to control, mostly by a significant reduction of ESV. PV-loop measurement revealed a marked 3.4-fold increase in ESPVR (systolic contractile function; p≤0.05). Arteriole density increased in the infarct zone (8.4 ± 0.9/mm2 in controls, versus 22.2±2.6/mm2 in the CellBeads group; p≤0.0001), capillary density increased in the border zone (908.1±99.7/mm2 in control animals versus 1209.0±64.6/mm2 in the CellBeads group; p≤0.05) and apoptosis was reduced in the infarct area (P≤0.05). Similar trends were observed in the moderate LCx AMI model.
Conclusion: Intracoronary infusion of CellBeads preserves contractile function and enhances angiogenesis after AMI. This promising new platform enables long-term local delivery of stem cells and cardioprotective proteins to the heart after acute myocardial infarction.
- © 2013 by American Heart Association, Inc.