Controlling Stem Cell Differentiation with GPCR Signals

Funding Type: 
Comprehensive Grant
Grant Number: 
RC1-00107
Investigator: 
ICOC Funds Committed: 
$0
oldStatus: 
Closed
Public Abstract: 
Heart disease is the leading killer of adults in the Western world. In addition, congenital heart malformations are the most common birth defects, occurring in nearly 1% of the population worldwide. A major goal of regenerative medicine is to repair damaged heart tissue. Our research is focused on developing new methods to stimulate human embryonic stem cells (hESCs) to form specific tissues to repair diseased heart tissue. There is growing optimism that cell-based therapies can repair damaged hearts. Although heart regeneration is minimal in humans, many animals show remarkable heart regeneration in response to a wide variety of injuries. Several clinical researchers have begun human clinical trials of cell preparations from muscle and bone marrow. The first small clinical trials yielded mixed results, and larger controlled trials are still in progress. The therapeutic action (if any) of these early attempts at cell therapy is unknown, and most investigators agree that more basic research is needed so that rational approaches to therapy can be devised. Most theories of heart regeneration focus on early cardiac progenitor cells, which are also the focus of our research plan. To devise new approaches to repair damaged heart tissue, we must learn more about the molecular “wiring” that is required to change hESCs into heart cells. We are using hESCs to examine how G-protein-coupled receptor (GPCR) signaling influences key cell developmental decisions required for proper heart formation. GPCRs, the largest class of cell-surface receptors, are ideal therapeutic targets. Although some GPCRs are the focus of intense pharmacological research, their potential for additional uses has not been explored fully. Specific drugs are lacking for >80% of GPCRs. Nevertheless, we can use genetic tools to “turn on” and “turn off” specific receptor signals at key times in development. These studies will reveal the GPCRs that would be most ideal for developing new drugs for regenerative medicine. The goal of our studies is to eventually improve the overall health of Californians. Heart disease remains a major cause of death and disability, resulting in billions of dollars in health care costs and lost days at work. Cardiac regeneration could dramatically improve recovery from heart disease such as heart attacks. This would improve the quality of life and increase productivity for millions of people worldwide. Additionally, this study will contribute to building the California economy by producing new technologies for the biotechnology industry.
Statement of Benefit to California: 
Heart disease is the leading killer of adults in the Western world. In addition, congenital heart malformations are the most common birth defects, occurring in nearly 1% of the population worldwide. A major goal of regenerative medicine is to repair damaged cardiac tissue. Our research is focused on developing new methods to differentiate human embryonic stem cells (hESCs) into specific cell types for cardiac regeneration. Our research could benefit the California economy by creating jobs in the biomedical industry by developing new technology. Ultimately, this study could help reduce heart disease, thereby increasing the productivity and enhancing the quality of life of Californians. The results of our studies will help develop new technology that could contribute to the California biotechnology industry. Our studies will create multiple lines of hESCs that have genetic markers that turn on at specific time points. These cell lines could be valuable for biotechnology companies and researchers who are screening for drug compounds that will cause these developmental changes. Furthermore, we are working closely with California companies to develop new microscopes and analysis software that could be the basis for new product lines or new businesses. If therapies do come to fruition, we anticipate that California medical centers will be leading the way. The most important contribution of this study will be to improve the health of Californians. Heart disease is a major cause of mortality and morbidity, resulting in billions of dollars in health care costs and lost days at work. Heart failure—the loss of cardiac pumping ability—results in a chronic debilitating disease that lasts for years. Cardiac regeneration could dramatically reduce heart disease worldwide. Our goal is to contribute research that would ultimately improve the quality of life and increase productivity for millions of people who suffer from heart disease. Our studies will also help understand how currently available medications can affect normal human hearts. In addition to identifying potential heart-related side effects in current medications, we may also find new uses for medications in preventing heart disease or repairing damaged tissue. As we continue our efforts in medical research, we hope to one day unlock the secrets of heart development and repair. This knowledge will help medical researchers develop beneficial therapies beyond what is currently available and potentially improve the quality of life and life expectancy of patients who suffer from heart disease.

© 2013 California Institute for Regenerative Medicine