| 摘要 |
<p>Disclosed is a fully chemically defined, small molecule-mediated, directed differentiation system that promotes differentiation of stem cells, including embryonic stem cells, induced pluripotent stem cells, and adult stem cells, such as human forms of these stem cell types, to ventricular cardiomyocytes in a highly efficient, reproducible and scalable fashion. Molecular characterization revealed the cardiomyocytes' progression through the sequential stages of cardiac fate specification. Phenotypic and electrophysiological analysis illustrated the generation of a highly pure population of cardiomyocytes (greater than 90%) exhibiting the expected physiological characteristics and response to cardioactive compounds. These data indicate that the directed differentiation system, through small molecule-mediated manipulation of developmental signaling pathways, generates a nearly pure population of functional ventricular cardiomyocytes from pluripotent stem cells. The disclosed differentiation system provides a platform to perform large-scale pharmacological screenings and to provide a valuable source of each of cardiac progenitor cells and cardiomyocytes for cell replacement therapies in cardiac repair.</p> |
