title: Xenotransplantation of Human Cardiomyocyte Progenitor Cells Does Not Improve Cardiac Function in a Porcine Model of Chronic Ischemic Heart Failure. Results from a Randomized, Blinded, Placebo Controlled Trial.
abstract: BACKGROUND
  Recently cardiomyocyte progenitor cells (CMPCs) were successfully isolated from fetal and adult human hearts. Direct intramyocardial injection of human CMPCs (hCMPCs) in experimental mouse models of acute myocardial infarction significantly improved cardiac function compared to controls.
  
  
  OBJECTIVE
  Here, our aim was to investigate whether xenotransplantation via intracoronary infusion of fetal hCMPCs in a pig model of chronic myocardial infarction is safe and efficacious, in view of translation purposes.
  
  
  RESULTS
  We performed a randomized, blinded, placebo controlled trial. Four weeks after ischemia/reperfusion injury by 90 minutes of percutaneous left anterior descending artery occlusion, pigs (n = 16, 68.5 ± 5.4 kg) received intracoronary infusion of 10 million fetal hCMPCs or placebo. All animals were immunosuppressed by cyclosporin (CsA). Four weeks after infusion, endpoint analysis by MRI displayed no difference in left ventricular ejection fraction, left ventricular end diastolic and left ventricular end systolic volumes between both groups. Serial pressure volume (PV-)loop and echocardiography showed no differences in functional parameters between groups at any timepoint. Infarct size at follow-up, measured by late gadolinium enhancement MRI showed no difference between groups. Intracoronary pressure and flow measurements showed no signs of coronary obstruction 30 minutes after cell infusion. No premature death occurred in cell treated animals.
  
  
  CONCLUSIONS
  Xenotransplantation via intracoronary infusion of hCMPCs is feasible and safe, but not associated with improved left ventricular performance and infarct size compared to placebo in a porcine model of chronic myocardial infarction.
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Sanne J
authors.initials: SJ
authors.lastname: Jansen of Lorkeers
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Johannes M I H
authors.initials: JM
authors.lastname: Gho
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.|ICIN - Netherlands Heart Institute, Utrecht, the Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koudstaal
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center Utrecht, the Netherlands.
authors.forename: Gerardus P J
authors.initials: GP
authors.lastname: van Hout
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Peter Paul M
authors.initials: PP
authors.lastname: Zwetsloot
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Joep W M
authors.initials: JW
authors.lastname: van Oorschot
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center Utrecht, the Netherlands.
authors.forename: Esther C M
authors.initials: EC
authors.lastname: van Eeuwijk
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Tim
authors.initials: T
authors.lastname: Leiner
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center Utrecht, the Netherlands.
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.|ICIN - Netherlands Heart Institute, Utrecht, the Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: ICIN - Netherlands Heart Institute, Utrecht, the Netherlands.|Experimental Cardiology Laboratory, University Medical Center Utrecht, the Netherlands.
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.|ICIN - Netherlands Heart Institute, Utrecht, the Netherlands.
authors.forename: Steven A J
authors.initials: SA
authors.lastname: Chamuleau
mesh_terms: D000818:Animals; D002908:Chronic Disease; D006321:Heart / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D010919:Placebos; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013552:Swine; D014183:Transplantation, Heterologous; D016277:Ventricular Function, Left
chemical_list: D010919:Placebos