Role of cardiac extracellular microenvironment in stem cell maturation and survival
Heart failure following a heart attack continues to be the leading cause of death in the United States, and the rest of the western world. The limited ability of the adult human heart to regenerate after a heart attack has led to much excitement regarding the potential of human embryonic stem cells to form cardiac muscle to repair the heart as well as provide models of human heart disease in a dish. This has, however, not yet been achieved because the cardiac muscle cells that are formed from human embryonic stem cells are immature and have poor survival upon transplantation in the heart. We hypothesize that the natural framework of the heart, the extracellular matrix, plays a key role in promoting survival and maturation of these cells. We have isolated this cardiac extracellular matrix from both adult human and porcine hearts and will use this as a platform to study the matrix effects on cardiac cell survival and maturation in a dish as well as in a rodent heart attack model. If successful, our studies will significantly advance the cardiac stem cell and regenerative medicine fields by using tissue engineering approaches to create an appropriate model system to understand the basic mechanisms underlying cardiac related survival, differentiation, maturation and function, with the potential development of a minimally invasive tissue engineering stem cell-based therapy for heart attacks and heart failure.
Heart failure following a heart attack is the leading cause of death in the United States, and in California. Other than heart transplantation for end-stage heart failure, there are no effective therapies to treat myocardial infarction and heart failure. This results in a diminished quality of life and loss of life for millions of patients and an extreme burden on the U.S. health care system. With this work, we will better understand how to form mature cardiac muscle from human embryonic stem cells, which could enable the development of novel minimally invasive tissue engineering therapies for treating heart attacks and heart failure.