Expanding mouse ventricular cardiomyocytes through GSK-3 inhibition

Controlled proliferation of cardiomyocytes remains a major limitation in cell biology and one of the main underlying hurdles for true modern regenerative medicine. Here, a technique is described for robust expansion of early fetal-derived mouse ventricular cardiomyocytes on a platform usable for high-throughput molecular screening, tissue engineering and, potentially, in vivo translational experiments. This method provides a small-molecule approach to control proliferation or differentiation of early beating cardiomyocytes through modulation of the Wnt/β-catenin signaling pathway. Moreover, isolation and expansion of fetal cardiomyocytes takes less than 3 weeks, yields a relatively pure (∼70%) functional myogenic population, and is highly reproducible.