TY - JOUR
T1 - Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells
AU - Mummery, Christine
AU - Ward-van Oostwaard, Dorien
AU - Doevendans, Pieter
AU - Spijker, Rene
AU - van den Brink, Stieneke
AU - Hassink, Rutger
AU - van der Heyden, Marcel
AU - Opthof, Tobias
AU - Pera, Martin
AU - de la Riviere, Aart Brutel
AU - Passier, Robert
AU - Tertoolen, Leon
PY - 2003
Y1 - 2003
N2 - Cardiomyocytes derived from human embryonic stem (hES) cells could be useful in restoring heart function after myocardial infarction or in heart failure. Here, we induced cardiomyocyte differentiation of hES cells by a novel method and compared their electrophysiological properties and coupling with those of primary human fetal cardiomyocytes. hES cells were cocultured with visceral-endoderm (VE)-like cells from the mouse. This initiated differentiation to beating muscle. Sarcomeric marker proteins, chronotropic responses, and ion channel expression and function were typical of cardiomyocytes. Electrophysiology demonstrated that most cells resembled human fetal ventricular cells. Real-time intracellular calcium measurements, Lucifer yellow injection, and connexin 43 expression demonstrated that fetal and hES-derived cardiomyocytes are coupled by gap junctions in culture. Inhibition of electrical responses by verapamil demonstrated the presence of functional alpha1c-calcium ion channels. This is the first demonstration of induction of cardiomyocyte differentiation in hES cells that do not undergo spontaneous cardiogenesis. It provides a model for the study of human cardiomyocytes in culture and could be a step forward in the development of cardiomyocyte transplantation therapies
AB - Cardiomyocytes derived from human embryonic stem (hES) cells could be useful in restoring heart function after myocardial infarction or in heart failure. Here, we induced cardiomyocyte differentiation of hES cells by a novel method and compared their electrophysiological properties and coupling with those of primary human fetal cardiomyocytes. hES cells were cocultured with visceral-endoderm (VE)-like cells from the mouse. This initiated differentiation to beating muscle. Sarcomeric marker proteins, chronotropic responses, and ion channel expression and function were typical of cardiomyocytes. Electrophysiology demonstrated that most cells resembled human fetal ventricular cells. Real-time intracellular calcium measurements, Lucifer yellow injection, and connexin 43 expression demonstrated that fetal and hES-derived cardiomyocytes are coupled by gap junctions in culture. Inhibition of electrical responses by verapamil demonstrated the presence of functional alpha1c-calcium ion channels. This is the first demonstration of induction of cardiomyocyte differentiation in hES cells that do not undergo spontaneous cardiogenesis. It provides a model for the study of human cardiomyocytes in culture and could be a step forward in the development of cardiomyocyte transplantation therapies
U2 - https://doi.org/10.1161/01.CIR.0000068356.38592.68
DO - https://doi.org/10.1161/01.CIR.0000068356.38592.68
M3 - Article
C2 - 12742992
SN - 0009-7322
VL - 107
SP - 2733
EP - 2740
JO - Circulation
JF - Circulation
IS - 21
ER -