BACKGROUND The proliferation of cardiomyocytes is highly restricted after postnatal maturation, limiting heart regeneration. Elucidation of the regulatory machineries for the proliferation and growth arrest of cardiomyocytes is imperative. Chemical biology is efficient to dissect molecular mechanisms of various cellular events and often provides therapeutic potentials. We have been investigatin...

Purification of cardiomyocytes from the embryonic mouse heart, embryonic stem (ES) or induced pluripotent stem cells (iPS) is a challenging task and will require specific isolation procedures. Lately the significance of surface markers for the isolation of cardiac cell populations with fluorescence activated cell sorting (FACS) has been acknowledged, and the hunt for cardiac specific markers ha...

RATIONALE Human embryonic and induced pluripotent stem cells (hESCs/hiPSCs) are promising cell sources for cardiac regenerative medicine. To realize hESC/hiPSC-based cardiac cell therapy, efficient induction, purification, and transplantation methods for cardiomyocytes are required. Though marker gene transduction or fluorescent-based purification methods have been reported, fast, efficient and...

Fine M, Lu FM, Lin MJ, Moe O, Wang HR, Hilgemann DW. Human-induced pluripotent stem cell-derived cardiomyocytes for studies of cardiac ion transporters. Am J Physiol Cell Physiol 305: C481–C491, 2013. First published June 26, 2013; doi:10.1152/ajpcell.00143.2013.— Human-induced pluripotent stem cells (hiPSCs) can differentiate into functional cardiomyocytes (iCell Cardiomyocytes) with ion chann...

Long QT syndrome (LQTS) is caused by functional alterations in cardiac ion channels and is associated with prolonged cardiac repolarization time and increased risk of ventricular arrhythmias. Inherited type 2 LQTS (LQT2) and drug-induced LQTS both result from altered function of the hERG channel. We investigated whether the electrophysiological characteristics of LQT2 can be recapitulated in vi...

We previously reported a point mutation substituting Cys for Arg(111) in the highly conserved troponin T (TnT)-contacting helix of cardiac troponin I (cTnI) in wild turkey hearts (Biesiadecki et al. J Biol Chem 279: 13825-13832, 2004). This dominantly negative TnI-TnT interface mutation decreases the binding affinity of cTnI for TnT, impairs diastolic function, and blunts the β-adrenergic respo...

Purpose: There are ongoing arguments as to how cardiomyocytes are aggregated together within the ventricular walls. We used pneumatic distension through the coronary arteries to exaggerate the gaps between the aggregated cardiomyocytes, analyzing the pattern revealed using computed tomography, and validating our findings by histology. Methods: We distended 10 porcine hearts, arresting 4 in dias...

BACKGROUND Despite the accumulating genetic and molecular investigations into hypertrophic cardiomyopathy (HCM), it remains unclear how this condition develops and worsens pathologically and clinically in terms of the genetic-environmental interactions. Establishing a human disease model for HCM would help to elucidate these disease mechanisms; however, cardiomyocytes from patients are not easi...

T he mammalian heart has a limited capacity for regeneration after damage. In contrast, teleost fish and urodelian amphibians readily regenerate even large cardiac defects. One of the central differences between species capable and incapable of efficient heart regenera-tion is the ability to reinitiate cardiomyocyte proliferation. The importance of cardiomyocyte proliferation for heart regenera...

The adult mammalian heart is one of the least regenerative organs, and therefore injury to this organ system results in a significant health and economic burden globally. Although it has been shown that a low level of cardiomyocyte turnover does occur in adult mammals, it is not sufficient to induce functional recovery in the damaged heart. In contrast, some vertebrate species (including zebraf...