Wnt3a-Induced Mesoderm Formation and Cardiomyogenesis in Human Embryonic Stem Cells

Authors


  • Author contributions: T.H.T.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; X.W.: technical support, manuscript review; C.B.: technical support, manuscript review; Y.Z.: collection and assembly of data, data analysis and interpretation; M.S.: data analysis and interpretation, manuscript review; S.I.: financial support, administrative support, manuscript review; M.B.: conception and design, financial support, administrative support, data analysis and interpretation, manuscript writing, final approval of manuscript.

  • First published online in STEM CELLS EXPRESS April 23, 2009.

Abstract

In vitro differentiation of human embryonic stem cells (hESCs) into pure human cardiomyocytes (hESCMs) would present a powerful tool to further the creation of cell models designed to advance preclinical drug development. Here, we report a novel differentiation method to substantially increase hESCM yield. Upon early and transient treatment of hESCs with Wnt3a, embryoid body and mesendoderm formation is enhanced, leading to greater differentiation toward cardiomyocytes. Moreover, the generated beating clusters are highly enriched with cardiomyocytes (50%) and express genes characteristic of cardiac cells, providing evidence that these hESCMs are competent to develop in vitro into functional and physiologically relevant cardiomyocytes. In summary, this protocol not only has the potential to guarantee a renewable supply of enriched cardiomyocyte populations for developing novel and more predictive cell models, but it also should provide valuable insights into pathways critical for cardiac regeneration. STEM CELLS 2009;27:1869–1878

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