Wednesday, March 24, 2010

FSSHH: Friday April 2 5pm Traylor 709 Med Campus

Presenter: Susan Thompson

Title: Human Embryonic Stem Cell Derived Cardiomyocytes Ameliorate Vulnerability for Arrhythmias in an In Vitro Model of Cardiac Fibrosis

Abstract: Human embryonic stem cells (hESCs) are an attractive candidate for cardiac regeneration because of their potential to supply a large number of differentiated cardiomyocytes that can integrate into the host tissue, thereby replacing the myocytes lost during myocardial aging, disease or damage. Numerous studies have already demonstrated improved myocardial function with grafts of human embryonic stem cell-derived cardiomyocytes (hESC-CMs), alluding to possible roles of paracrine effects and direct myocardial regeneration. However, little attention has been given to the electrophysiological benefit that these cells may have on diseased myocardium, and specifically, on cardiac fibrosis, a pathological condition found in aging, heart failure, and myocardial infarction. We therefore set out to characterize the electrophysiological benefits of adding hESC-CMs to our previously reported, in vitro model of cardiac fibrosis. Following engraftment of hESC-CMs from beating hESC-CMs, LCV and TCV of fibrotic monolayers increased to 39.3±2.7 and 12.5±1.3 cm/s, respectively (n=6). In contrast, addition of hESCs from non-beating EBs suppressed LCV and TCV to 6.5±1.3 and 2.1±1 cm/s, respectively (n=4). We show for the first time that hESC-CMs reverse the loss of conduction velocity and reduce the incidence of spiral waves in an in vitro fibrosis model. This finding is significant in that it suggests that specifically hESC-CMs can directly participate in electrical propagation, perhaps through gap junction coupling, and can ameliorate abnormal conduction in fibrotic myocardium.