This technology increases the number of cardiomyocytes produced using embryonic stem (ES) cells and may be used for the treatment of cardiovascular disease.
Cardiomyocytes generated from ES cells in vitro have successfully survived, fused with surrounding tissue, and been retained in animal hosts making them ideal candidates for clinical transplantation therapy. In order for these clinical applications to come to fruition, sufficient numbers of cardiomyocytes need to be produced. This invention describes methods to increase the production of cardiomyocytes from ES cells and create cell culture populations enriched in cardiomyocytes.
ES cells exposed to low oxygen levels for an extended period of time differentiate into cardiomyocytes even in the absence of exogenously added growth factors and agents. First, cells are cultured at an oxygen partial pressure lower than atmospheric partial pressure over two to eight days. A second culture step may be further pursued in which the oxygen partial pressure is subsequently raised for another two to eight days. This simple method generates on average sixty cardiomyocytes from a single ES cell and allows for cell populations with a higher proportion of cardiomyocytes.
- Increases the number of cardiomyocytes and cardiomyocyte progenitors
method produces cardiomyocyte enriched populations without cardiomyocyte
need for exogenous agents to promote differentiation