Year 1

Heart failure affects an estimated 5.8 million Americans with about half a million new cases every year. It is also one of the leading causes of death and loss of productivity in California. There is a clear unmet medical need to develop new therapies to treat patients with heart failure. Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and retain the pluripotency to differentiate into all cell types in the body. Therefore, as a renewable source of various cell types in the body, hESCs hold great promise for the cell replacement therapy of many human diseases. In this context, significant progress has been made in the differentiation of hESCs into functional cardiomyocytes (CMs), providing the potential of cell replacement therapy to cure heart diseases through the restoration of lost cardiac function. However, one key bottleneck hindering the clinic development of hESC-derived CMs is that hESC-derived CMs will be rejected by allogenic immune system of the recipients, and the typical immunosuppressant regimen can be highly toxic for patients with heart diseases. To resolve this bottleneck and improve the feasibility of the hESC-based therapy of heart failure, we developed and validated a novel approach to protect the hESC-derived CMs from the allogenic human immune system in vivo.