Heart failure is a major disease in California with limited therapeutic options. It costs the State tremendous expenditure in treatment and loss in productivity. While heart transplant is effective in treating the disease, this option is limited by the scarcity of heart donors and the modest graft survival rate (50%) ten years after transplantation. With their unlimited self-renewal capability and pluripotency to differentiate into all cell types in the body, human ES cells (hESCs) hold great promise for human cell therapy. Therefore, cell therapy approaches with hESC-derived CMs have the unique potential for a cure by restoring lost CMs and cardiac function. Despite significant progress in differentiating hESCs into CMs that are capable of partially restoring heart functions in myocardia infarction (MI) animal models, one key bottleneck remaining is that the allogenic hESC-derived CMs will be immune rejected by the recipients, and the typical immunosuppression regimen is especially toxic for patients with advanced heart diseases. By developing a novel approach to prevent allogenic immune rejection of hESC-derived CMs without the typical immunosuppression, we showed that genetically modified hESCs can be efficiently differentiated into cardiomyocytes, which exhibit characteristic electric physiological properties and are protected from allogenic immune rejection.