Expanding mouse ventricular cardiomyocytes through GSK-3 inhibition

通过抑制GSK-3来扩增小鼠心室心肌细胞

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作者:Jan W Buikema, Peter-Paul M Zwetsloot, Pieter A Doevendans, Joost P G Sluijter, Ibrahim J Domian

Abstract

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.

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