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

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. Here, our a...

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Bibliographic Details
Published in:PloS one 2015-12, Vol.10 (12), p.e0143953-e0143953
Main Authors: Jansen of Lorkeers, Sanne J, Gho, Johannes M I H, Koudstaal, Stefan, van Hout, Gerardus P J, Zwetsloot, Peter Paul M, van Oorschot, Joep W M, van Eeuwijk, Esther C M, Leiner, Tim, Hoefer, Imo E, Goumans, Marie-José, Doevendans, Pieter A, Sluijter, Joost P G, Chamuleau, Steven A J
Format: Article
Language:English
Subjects:
Animal models
Animals
Bone marrow
Cardiology
Cardiomyocytes
Care and treatment
Cell death
Cells (biology)
Chronic Disease
Chronic illnesses
Complications and side effects
Development and progression
Echocardiography
Fetuses
Gadolinium
Health aspects
Heart
Heart - physiopathology
Heart attacks
Heart diseases
Heart failure
Heart transplantation
Infarction
Infusion
Ischemia
Laboratory animals
Magnetic Resonance Imaging
Medical research
Myocardial infarction
Myocardial Ischemia - physiopathology
Myocardial Ischemia - therapy
Myocytes, Cardiac - cytology
NMR
Nuclear magnetic resonance
Occlusion
Patient outcomes
Pigs
Placebos
Pressure
Progenitor cells
Randomization
Reperfusion
Smooth muscle
Stem Cell Transplantation
Stem cells
Stem Cells - cytology
Swine
Systematic review
Transplantation, Heterologous
Ventricle
Ventricular Function, Left
Xenografts
Xenotransplantation
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Summary: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. 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. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0143953