Wnt3a-induced mesoderm formation and cardiomyogenesis in human embryonic stem cells.
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.
Tran
Thanh H
TH
Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA.
Wang
Xiurong
X
Browne
Carol
C
Zhang
Yunyu
Y
Schinke
Martina
M
Izumo
Seigo
S
Burcin
Mark
M
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods*; D051153:Wnt Proteins / Q000494:pharmacology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D007328:Insulin; D011994:Recombinant Proteins; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse