Introduction: 

ABC transporters are well known to extrude a variety of xenobiotic substances from tissues and have been used to identify specific sub-populations of stem cells. The physiological meaning of ABC transporters for the maintenance of stemness and cardiac differentiation processes is so far unkown.

Objectives: 

To investigate the effects of either pharmacological inhibition or si-RNA-mediated knockdown of ABCB1 and ABCG2 on cardiomyogenesis of mouse embryonic (ES) cells.

Methods and Results: 

Embryoid bodies differentiated from ES cells expressed both ABCB1 and ABCG2. The ABC transporters were functional as evaluated by doxorubicin efflux studies. Treatment of differentiating embryoid bodies either with the ABCB1-specific inhibitor zosuquidar or the ABCG2-specific inhibitor Ko-143 significantly increased the number of contracting cardiac foci and cardiac cell areas. Furthermore increased cardiomyogenesis was observed upon siRNA-mediated downregulation of ABCB1 and ABCG2. This treatment significantly upregulated ROS generation in embryoid bodies which is well known to stimulate cardiomyogenesis of ES cells.

Conclusions: 

Inhibition of ABC transporter function and/or genetic downregulation of ABC transporter expression stimulates cardiomyogenesis of ES cells presumably by increasing ROS production.