Electrical Integration of Human Embryonic Stem Cell-Derived Cardiomyocytes in a Guinea Pig Chronic Infarct Model

作者：Yuji Shiba, Dominic Filice, Sarah Fernandes, Elina Minami, Sarah Dupras, Benjamin Van Biber, Peter Trinh, Yusuke Hirota, Joseph Gold, Mohan Viswanathan, Michael A. Laflamme · 发表于：Journal of Cardiovascular Pharmacology and Therapeutics · 年份：2014 · DOI：10.1177/1074248413520344 · 被引用次数：114 · 研究领域：Pluripotent Stem Cells Research、Planarian Biology and Electrostimulation、Mesenchymal stem cell research

BACKGROUND: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were recently shown to be capable of electromechanical integration following direct injection into intact or recently injured guinea pig hearts, and hESC-CM transplantation in recently injured hearts correlated with improvements in contractile function and a reduction in the incidence of arrhythmias. The present study was aimed at determining the ability of hESC-CMs to integrate and modulate electrical stability following transplantation in a chronic model of cardiac injury. METHODS AND RESULTS: At 28 days following cardiac cryoinjury, guinea pigs underwent intracardiac injection of hESC-CMs, noncardiac hESC derivatives (non-CMs), or vehicle. Histology confirmed partial remuscularization of the infarct zone in hESC-CM recipients while non-CM recipients showed heterogeneous xenografts. The 3 experimental groups showed no significant difference in the left ventricular dimensions or fractional shortening by echocardiography or in the incidence of spontaneous arrhythmias by telemetric monitoring. Although recipients of hESC-CMs and vehicle showed a similar incidence of arrhythmias induced by programmed electrical stimulation at 4 weeks posttransplantation, non-CM recipients proved to be highly inducible, with a ∼3-fold greater incidence of induced arrhythmias. In parallel studies, we investigated the ability of hESC-CMs to couple with host myocardium in chronically injured hearts by the intravital imaging of ...