title: Intracoronary infusion of encapsulated glucagon-like peptide-1-eluting mesenchymal stem cells preserves left ventricular function in a porcine model of acute myocardial infarction.
abstract: 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).
  
  
  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 either intracoronary 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(2) in controls versus 22.2±2.6/mm(2) in eMSC group; P<0.001). Although not statistically significant, capillary density was 30% higher in the border zone (908.1±99.7/mm(2) in control versus 1209.0±64.6/mm(2) 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.
authors.affiliation: From the Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands (R.d.J., J.H.H., K.K.); Experimental Cardiology Laboratory, University and Medical Center Utrecht, The Netherlands (G.P.J.v.H., G.P., I.E.H.); BTG International Germany GmbH, Alzenau, Germany (C.W.); Biocompatibles UK Ltd, a BTG International Group Company, Farnham, United Kingdom (A.L.); and Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (H.J.D.).
authors.forename: Renate
authors.initials: R
authors.lastname: de Jong
authors.affiliation: From the Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands (R.d.J., J.H.H., K.K.); Experimental Cardiology Laboratory, University and Medical Center Utrecht, The Netherlands (G.P.J.v.H., G.P., I.E.H.); BTG International Germany GmbH, Alzenau, Germany (C.W.); Biocompatibles UK Ltd, a BTG International Group Company, Farnham, United Kingdom (A.L.); and Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (H.J.D.).
authors.forename: Gerardus P J
authors.initials: GP
authors.lastname: van Hout
authors.affiliation: From the Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands (R.d.J., J.H.H., K.K.); Experimental Cardiology Laboratory, University and Medical Center Utrecht, The Netherlands (G.P.J.v.H., G.P., I.E.H.); BTG International Germany GmbH, Alzenau, Germany (C.W.); Biocompatibles UK Ltd, a BTG International Group Company, Farnham, United Kingdom (A.L.); and Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (H.J.D.).
authors.forename: Jaco H
authors.initials: JH
authors.lastname: Houtgraaf
authors.affiliation: From the Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands (R.d.J., J.H.H., K.K.); Experimental Cardiology Laboratory, University and Medical Center Utrecht, The Netherlands (G.P.J.v.H., G.P., I.E.H.); BTG International Germany GmbH, Alzenau, Germany (C.W.); Biocompatibles UK Ltd, a BTG International Group Company, Farnham, United Kingdom (A.L.); and Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (H.J.D.).
authors.forename: Kushan
authors.initials: K
authors.lastname: Kazemi
authors.affiliation: From the Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands (R.d.J., J.H.H., K.K.); Experimental Cardiology Laboratory, University and Medical Center Utrecht, The Netherlands (G.P.J.v.H., G.P., I.E.H.); BTG International Germany GmbH, Alzenau, Germany (C.W.); Biocompatibles UK Ltd, a BTG International Group Company, Farnham, United Kingdom (A.L.); and Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (H.J.D.).
authors.forename: Christine
authors.initials: C
authors.lastname: Wallrapp
authors.affiliation: From the Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands (R.d.J., J.H.H., K.K.); Experimental Cardiology Laboratory, University and Medical Center Utrecht, The Netherlands (G.P.J.v.H., G.P., I.E.H.); BTG International Germany GmbH, Alzenau, Germany (C.W.); Biocompatibles UK Ltd, a BTG International Group Company, Farnham, United Kingdom (A.L.); and Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (H.J.D.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Lewis
authors.affiliation: From the Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands (R.d.J., J.H.H., K.K.); Experimental Cardiology Laboratory, University and Medical Center Utrecht, The Netherlands (G.P.J.v.H., G.P., I.E.H.); BTG International Germany GmbH, Alzenau, Germany (C.W.); Biocompatibles UK Ltd, a BTG International Group Company, Farnham, United Kingdom (A.L.); and Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (H.J.D.).
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: From the Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands (R.d.J., J.H.H., K.K.); Experimental Cardiology Laboratory, University and Medical Center Utrecht, The Netherlands (G.P.J.v.H., G.P., I.E.H.); BTG International Germany GmbH, Alzenau, Germany (C.W.); Biocompatibles UK Ltd, a BTG International Group Company, Farnham, United Kingdom (A.L.); and Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (H.J.D.).
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.affiliation: From the Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands (R.d.J., J.H.H., K.K.); Experimental Cardiology Laboratory, University and Medical Center Utrecht, The Netherlands (G.P.J.v.H., G.P., I.E.H.); BTG International Germany GmbH, Alzenau, Germany (C.W.); Biocompatibles UK Ltd, a BTG International Group Company, Farnham, United Kingdom (A.L.); and Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands (H.J.D.). h.j.duckers@umcutrecht.nl.
authors.forename: Henricus J
authors.initials: HJ
authors.lastname: Duckers
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D004452:Echocardiography; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007261:Infusions, Intra-Arterial; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D013552:Swine; D019076:Transgenes / Q000235:genetics; D016277:Ventricular Function, Left
chemical_list: D052216:Glucagon-Like Peptide 1
keywords: acute anterior wall myocardial infarction; acute myocardial infarction; cell therapy; glucagon-like peptide-1; mesenchymal stromal cells; percutaneous coronary intervention