Abstract 9277: Transplantation of Mesenchymal Stem Cells Mitigates Cardiac Electrophysiological Remodelling in a Rat Model of Myocardial Infarction
Background: Cell transplantation is a promising therapy for heart failure, demonstrating modest improvements in cardiac function in clinical trials, but the underlying mechanism of the therapeutic benefits is not yet fully elucidated. The aim of this study was to 1) evaluate the electrophysiological impacts of transplanted mesenchymal stem cells (MSC) on infarcted heart tissues and 2) correlate electrophysiological changes with donor cell survival and gene expression in the host myocardium.
Methods: Three weeks after coronary ligation to induce myocardial infarction (MI) in Lewis rats, 3×106 MSC or culture medium were directly injected into each infarct. One to two weeks later, hearts were excised, Langendorff-perfused, and optically mapped using a potentiometric fluorescent dye (di-4-ANEPPS), high-speed CMOS cameras (100×100 pixels, 1 kHz samp/s, 0.4 mm/pixel) and custom software designed to measure various cardiac electrical parameters. Hearts were then sectioned for morphometric and histological analyses. Vascular density was determined by counting Factor VIII-immunopositive structures observed in histological sections. Gene expression was assessed by qRT-PCR. Male MSC survival in female hearts was evaluated by qPCR for the Y-chromosomal gene sry.
Results: Optical mapping showed that MSC transplantation attenuated the reduction in conduction velocity and the protraction of effective refractory period in the host myocardium in our infarct model (Table). These electrophysiological changes correlated with enhanced connexin43 expression, higher vascular density, and better-preserved ventricular geometry in MSC-injected hearts.
Conclusion: Apart from well-documented benefits such as restoring cardiac function, promoting angiogenesis and limiting adverse structural remodelling in infarcted hearts, MSC transplantation also mitigates electrophysiological remodelling and is thus a potential strategy to prevent post-MI arrhythmias.
- © 2010 by American Heart Association, Inc.