For the millions of Americans who are born with or develop heart disease, stem cell research offers the first real hope of reversing or repairing heart muscle damage. In addition to their regenerative potential, human stem cells offer an unprecedented opportunity to study mechanisms of human disease and develop and test novel therapies. However, these new applications are limited by the lack of culture conditions that replicate complex tissue structures. Theses limitations are particularly apparent for many cardiovascular diseases. Thus, there is a great need for laboratory biotechnologies that replicate the 3-D microenvironment and conditions seen in patients. We propose to create synthetic human heart muscle in culture with perfused bioreactors. Bioreactors are contained reaction vessels for the controlled culture of cells to create tissues in a dish. The models and knowledge gained from these studies will facilitate the creation of cardiovascular disease-in-a-dish models and systems to reliably screen new therapies.
Statement of Benefit to California:
Heart disease, stroke and other cardiovascular diseases are the #1 killer in California. Despite medical advances, heart disease remains a leading cause of disability and death. Recent estimates of its cost to the U.S. healthcare system amounts to almost $300 billion dollars. Although current therapies slow the progression of heart disease, there are few, if any options, to reverse or repair damage. Thus, regenerative therapies that restore normal heart function would have an enormous societal and financial impact not only on Californians, but the U.S. more generally. The research that is proposed in this application could lead to new therapies that would restore heart function after and heart attack and prevent the development of heart failure and death. We will develop the techniques and models that will allow the development and testing of cardiovascular therapies. Combining tissue engineering with disease-specific human pluripotent stem cells will facilitate the creation of cardiovascular disease-in-a-dish models and systems to reliably screen new therapies.