1. Field of the Invention
The present invention relates generally to the field of stem cell development. More particularly, it concerns the induction of cardiomyocyte differentiation from pluripotent stem cells.
2. Description of Related Art
Cardiomyocytes are thought to be terminally differentiated. Although a small percentage of cardiomyocytes may have proliferative capacity, this is not sufficient to adequately replace injured or dead cardiomyocytes. Death of cardiomyocytes occurs, for example, when a coronary vessel is occluded by a thrombus and the surrounding cardiomyocytes cannot be supplied with necessary energy sources from other coronary vessels. Loss of functional cardiomyocytes may lead to chronic heart failure.
The proliferative capacity of the cardiomyocytes is not sufficient to regenerate the heart following myocardial injury. Conventional pharmacological therapy for patients with different stages of ischemic heart disease improves cardiac function, survival and quality of life. However, ischemic heart disease is still the most life-threatening disease in the United States and Europe; accordingly, alternative therapies will be necessary to improve the clinical outcome for patients with ischemic heart disease further. In recent years, the focus on cell replacement therapy has been intensified, stimulated by the increasing number of potential cell sources for transplantation, such as skeletal myoblasts, adult cardiac stem cells, bone marrow stem cells and embryonic stem cells.
A potential route for restoring “normal” heart function is replacement of injured or dead cardiomyocytes by new functional cardiomyocytes. Pluripotent stem cells, such as human embryonic stem (ES) cells or induced pluripotent stem cells (iPS) cells, are a potential source of cells for cardiomyocyte replacement. Differentiation of pluripotent stem cells into cardiomyocytes can be achieved either spontaneously or upon induction.
However, a number of obstacles have stood in the way of developing a paradigm for obtaining substantially enriched populations of cardiomyocyte lineage cells from pluripotent stem cells. Some ensue from the relative fragility of pluripotent cells of primate origin, the difficulty in culturing them, their exquisite sensitivity and dependence on various factors present in the culture environment, and low efficiency and wide variation of differentiation methods. Thus, there is a need to improve induction of differentiation of pluripotent stem cells to cardiomyocytes, especially for large-scale production.