Inducing human embryonic stem cell differentiation into cardiomyocytes using extracellular matrix cues
Heart failure following a heart attack is the leading killer in the United States and is attributed to one out of every five deaths. Heart transplantation is a successful treatment, but there is a limited supply of donor organs and many patients die each year waiting for a heart. Since there is very limited regenerative capacity in the heart, researchers have investigated delivering adult cells in an attempt to replace damaged heart tissue, yet clinical success has not been achieved since these cell types do not match those in the heart. Cardiac muscle cells would be an ideal choice for cell transplantation, but adult cardiac cells do not replicate and thus a large supply cannot be grown. To overcome that limitation, we propose to develop a reliable method to direct human embryonic stem cells to form cardiac muscle cells using cues from the surface they are grown on. Human embryonic stem cells have the ability to become cardiac muscle cells, and are therefore an exciting possible cell source for transplantation to repair the heart after a heart attack. Prior to delivery, the cells must be directed to form cardiac muscle cells. A handful of studies have discovered soluble reagents that promote formation of cardiac muscle cells. Cell fate is not only determined by soluble factors, but by what the cells adhere to. Researchers know that cell adhesion mediates cell fate with adult cells, yet no studies have examined how the cell culture surface affects cardiac muscle cell formation from human embryonic stem cells. This proposal therefore aims to examine several surfaces to promote cardiac muscle cell formation, including the use of micro- and nanopatterned surfaces. With the knowledge gained from this research, cell transplantation for cardiac repair may become an available treatment for heart attacks in humans.
Human embryonic stem cells have the power to become any cell in the body. Being able to direct them into becoming cardiac muscle cells could allow them to become a treatment for heart failure following a heart attack, which is the leading killer in California. Bioengineering experimental studies proposed here will help create methods to direct human embryonic stem cells into cardiac muscle cells. Researchers have already derived cardiac muscle cells from embryonic stem cells, but methods to enhance and control this process must be developed before the cells can be used in humans. In our approach, bioengineering techniques may be able to create the right environment for the development of cardiac muscle cells. Material cues and specialized surfaces will be used to influence and control embryonic stem cell fate. With success, this technology could provide a cell source for repairing damaged heart tissue.
The lifetime risk of developing coronary heart disease after 40 is 49 percent for men and 32 percent for women. Moreover, approximately 38 percent of people who have a heart attack will die from it. It is estimated that this year approximately 700,000 Americans will have a new heart attack and an additional 500,000 will have a recurrent attack, with estimated direct and indirect costs of $151.6 billion. Considering the population of California is approximately 12% of the country, this equates to 84,000 new heart attacks and 60,000 recurrent attacks this year in the state, with an annual cost of $18.2 billion. Treatment using embryonic stem cell derived cardiac muscle cells could thus affect the lives of tens of thousands Californians each year. It would also reduce state health care costs associated with this disease.