Fig. 9.

In vitro differentiation of CMs from hiPSCs. Three main methods are documented for differentiation of hiPSCs into CMs. The most documented, directed cardiac differentiation, is achieved with sequential cytokine stimulation following the culture of hiPSCs in low adherent culture plates, forcing the cells to aggregate into so-called embryoid bodies. Alternatively, the same type of sequential cytokine stimulation was also proven successful when cells are kept in 2D conditions. Finally, a “natural” differentiation into CMs was documented following co-culture of hiPSCs with END-2 endothelial cells. CM cardiomyocyte, END-2 endodermal cell line-2, hiPSC human induced pluripotent stem cell