The mechanism of the multipotency of human cardiac progenitors
A major goal of the stem cell research is to regenerate the damaged human tissue by creating physiologically relevant cell types. Human stem cells and induced pluripotent stem cells provide us a promising source for the cardiomyocytes. Recent technological advances have made possible the transplantation of these cells and generation of biological cardiac sheet which could supplement the contractility of the failing heart. While researches towards the application of the stem cells are advancing rapidly, however, initial clinical trials suggest that their cardiac regeneration potential is controversial and that the functional benefits are modest. Further understanding of the basic biology of human cardiac differentiation is required before designing larger-scale trials.
Although recent progress in animal models has revealed the diversity of cardiovascular cell populations, we are at a relatively primitive stage in understanding how immature human stem cells give rise to diverse cell types in human cardiovascular system including atrial and ventricular myocardium, cardiac pacemaker cells, and the smooth muscle and endothelial cells in the vasculature. This project will elucidate the basic mechanism of cardiovascular cell diversification with the goal of future cell replacement therapy for regenerating the heart.
Our international research team comprise of medical scientists who have gained fundamental insight into cardiac differentiation from animal models, and researchers who have developed new technologies in genetically manipulating human stem cells. Combination of the expertise will enable us to analyze the basic cellular and molecular mechanism underlying the diversification of human cardiac populations at unprecedented resolution. Knowledge from this proposal will help understand disease mechanisms of congenital and adult heart diseases, and develop stem cell-based therapy for these diseases.
Heart disease and stroke are the first and the third leading causes of death in California and a major cause of disability. 40,000 Californians are admitted to hospitals because of heart attack, and 73,000 Californians die from heart disease and stroke each year, more than the total number of deaths in that year from cancer, diabetes, chronic liver disease/cirrhosis, suicide, homicide, and AIDS combined. Additionally, cardiovascular diseases impose an enormous economic burden on our State. The annual cost for heart disease and stroke is $300 billion to the U.S. and $48 billion to California alone. The cost will gradually increase because the number of deaths from cardiovascular diseases will undoubtedly increase as the State’s population ages. It is clear that novel therapeutic approaches are needed to halt the devastating consequences of heart disease and stroke. Stem cell-based regenerative technologies proposed in this study in partnership with international collaborators will provide a platform for the analysis of the mechanism of cardiac regeneration and a promise to repair the damaged myocardium. Now the whole stem cell research is progressing rapidly in the world, the exchange of information and organized activities of fundamental researches are becoming more and more important. The opportunity to bring in new ideas and essential technologies will help both Californian and Japanese scientific communities further expand and strengthen the stem cell research.