MicroRNA and Pluripotent Stem Cell-Based Heart Therapies: The Electrophysiological Perspective

Abstract

MicroRNAs (miRs) are nonencoding RNAs that function as negative transcriptional regulators via degradation or inhibition by RNA interference. Recent studies have demonstrated that miRs are important regulators of cardiovascular cell differentiation, growth, proliferation, and apoptosis. Specifically, miRs modulate electrophysiological properties such as automaticity, conduction, and membrane repolarization by regulating a wide range of target genes. Not surprisingly, dysregulation of miR function can lead to cardiovascular diseases. Indeed, abnormal miR expression patterns have been detected in hypertrophy and arrhythmias. Cardiomyocytes (CMs) are terminally differentiated and cannot regenerate. Therefore, significant loss of CMs due to disease or aging can lead to cardiac arrhythmias, heart failure, and subsequently death. Human embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency to differentiate into all cell types, including CMs. Therefore, hESCs may provide an unlimited ex vivo source of CMs for cell-based heart therapies. The process of deriving CMs from hESCs can be optimized by miR-directed differentiation and specification. When combined with stem cell biology, the emerging field of miR presents novel approaches for the improvement of many cardiac therapy strategies.