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 |
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| Authors: | Sanne J. Jansen of Lorkeers Johannes M. I. H. Gho Stefan Koudstaal Gerardus P. J. van Hout Peter Paul M. Zwetsloot Joep W. M. van Oorschot Esther C. M. van Eeuwijk Tim Leiner Imo E. Hoefer Marie-José Goumans Pieter A. Doevendans Joost P. G. Sluijter Steven A. J. Chamuleau |
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| Affiliation: | 1. Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.; 2. ICIN - Netherlands Heart Institute, Utrecht, the Netherlands.; 3. Experimental Cardiology Laboratory, University Medical Center Utrecht, the Netherlands.; 4. Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.; 5. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.; Georgia Regents University, UNITED STATES, |
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| Abstract: | BackgroundRecently 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.AimHere, 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.Methods & ResultsWe 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.ConclusionXenotransplantation 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. |
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