Human Embryonic Stem Cell for Myocardial Restoration

Funding Type: 
Comprehensive Grant
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Coronary artery disease (CAD) is the leading cause of death in the Western world and consumes approximately fifty billion dollars annually in the United States. CAD is the most common cause of congestive heart failure (CHF), which is now the leading diagnosis associated with hospital admission afflicting over 5 million people in this country. Despite aggressive treatment of CHF with advanced medical regimen and implantable devices, the average five-year survival is a dismal 50%. Congestive heart failure is primarily a disease of tissue loss, with an overall decrease in functional capacity and residual structural deformity that can further impair remaining pump function. Medical therapies to stimulate compensatory function of the remaining myocardial tissue and surgical attempts to remodel the remaining heart tissue have been largely unsuccessful. While regeneration approaches to the treatment of decompensated heart function have been attempted for some time, only recently has a source of cellular building blocks with demonstrable ability to generate functional heart tissue become widely available, human embryonic stem cells (hESCs). This Program brings together a committed group of physicians and scientists at {REDACTED} who share a keen interest in the basic research of regeneration and functional restoration of cardiac tissue, and who firmly believe that the ultimate outcome of this collaboration will be the transplantation of hESC-derived cells for the treatment of human heart disease. The leaders of the various portions of this proposal have complementary strengths, which include expertise in stem cell biology and stem cell purification, in vivo assays that assess cardiac repair, histology and specialized microscopy, and state of the art imaging of small and large animals, as well as humans. We have come together to answer the critical questions that need to be addressed prior to investigation of this approach in human clinical studies. The work proposed in this application will teach us how to isolate the heart cells that spontaneously form from hESC when they differentiate in the laboratory, how to track and optimize survival of the hESC-derived heart cells, and how to delivery the cells and monitor their function in large animal models of heart disease. Upon completion of the proposed work, we will have established a rational protocol for the safe clinical study of embryonic stem cell therapy as a treatment of end-stage congestive heart failure

Statement of Benefit to California: 

Coronary artery disease (CAD) is the leading cause of death in California and consumes approximately 6 billion dollars annually in this state, representing a large portion of our annual health care budget. One of the common causes of death from CAD is congestive heart failure (CHF). CHF is now the leading diagnosis associated with hospital admission in this state, afflicting over 550,000 people in California. Despite aggressive treatment of CHF with advanced medical regimens and implantable devices, the average five-year survival is a dismal 50%, even in the finest tertiary heart care centers in this state. Cardiac transplantation is an established treatment for end-staged CHF but is limited to a few hundred patients per year in California. The benefit to citizens of California of the work proposed in this application is the development of tools and methodology leading to a novel and effective treatment for CHF. This treatment will be the replacement or regeneration of dead or diseased heart tissue with new and functional tissue that is derived from human embryonic stem cells. While there is still some debate, most scientists now believe that such cells are the only possible source for replacement heart tissue. Many issues need to be addressed before such therapy can be implemented. The scientists at {REDACTED} who have created this application are experts in the areas of research and clinical care that are required to create the replacement tissues, deliver the tissues to the injured heart, and monitor the treatment to optimize clinical utility.