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.
Highlights
The heart has regenerative capacity as it harbours a pool of cardiac stem cells.[1]
Xenotransplantation via intracoronary infusion of human cardiomyocyte progenitor cells (CMPC) (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
Our lab succeeded in isolating fetal and adult cardiomyocyte progenitor cells (CMPC) from mouse and human hearts based on the stem cell antigen Sca-1.[2]. CMPCs can successfully been differentiated in cardiomyocytes, endothelial cells and smooth muscle cells in vitro. [2,3,4] These hCMPC-derived cardiomyocytes have functional gap junctions, enabling metabolic and electrical coupling of cells.[4]
Summary
The heart has regenerative capacity as it harbours a pool of cardiac stem cells.[1]. this is clearly not sufficient to repair the damage caused by myocardial infarction (MI) to prevent the development of heart failure. Our lab succeeded in isolating fetal and adult cardiomyocyte progenitor cells (CMPC) from mouse and human hearts based on the stem cell antigen Sca-1.[2] CMPCs can successfully been differentiated in cardiomyocytes, endothelial cells and smooth muscle cells in vitro. [2,3,4] These hCMPC-derived cardiomyocytes have functional gap junctions, enabling metabolic and electrical coupling of cells.[4] Intra-myocardial injection of hCMPCs in a mouse model of acute MI led to engraftment of 3,5% of cells, differentiation towards coupled cardiomyocytes, increased vascular density, and to improved cardiac function. 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
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