Stem Cell Transplantation Induces a Rapid Change in Cardiac Excitability

Embryonic (ES) and bone marrow derived stem cells are discussed as a potential source for cardiac replacement tissue. Transplantation of undifferentiated cells into the cardiac infarct region has been shown to decrease infarct size and preserve cardiac function. Long term studies determined homing of stem cells in the cardiac muscle, the immediate impact of cell transplantation on the electrophysiological properties of however remains unclear. To determine if the time course in which stem cells establish intercellular coupling we plated Calcein/AM loaded ES cells on monolayers of cardiomyocytes (HL-1 cells). Dye transfer that was monitored by confocal microscopy, was first observed 60 min after heterocellular culture was established. It could be blocked by carbenoxolone indicating the presence of gap junction channels. After 200 min 36 ± 7% of ES cells had established intercellular coupling with cardiomyocytes. To determine the impact of cell transplantation on the electrophysiological properties we established monolayers on multielectrode arrays (MEAs). From field potential measurements we determined that induction of co-culture resulted in a biphasic change of the electrophysiological properties. During the first 45 min an increase of the conduction velocity (CV: 142 ± 17 %) and of the spontaneous beating frequency (F: 172 ± 11%) could be detected (n = 10). With further progression of co-culture however, a continuous decrease of excitability occurred (180min; F: 31 ± 3%; CV: 50 ± 2.5%) that ultimately resulted in the loss of spontaneous activity (210 min). In control cultures no biphasic change in F or CV was observed. The data indicate that stem cell transplantation results in rapid heterocellular coupling between stem cells and cardiomyocyte and a suppression of cardiac excitability. The contribution of intercellular coupling and other paracrine mechanism to the change in excitability remains to be determined.