Year 3

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 cardiomyocytes (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 myocardial infarction (MI) animal models, one key bottleneck remaining is that the non recipient matched, or 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. Our research effort is to develop a novel approach to prevent allogenic immune rejection of hESC-derived CMs without the typical immunosuppression that induces systemic immune suppression.

We have developed hESC-CM that are resistant to allogeneic rejection and confirmed this property by performing allogeneic transplants using a humanized mouse model. This data suggests that our hESC-CM may act as universal donor heart cells for transplants into patients’ hearts. The ability of these cells to improve function of injured hearts will be tested in a preclinical model of myocardial infarction. This test will confirm the feasibility of our development candidate for further translation .”