| Cell transplantation is emerging as a promising new approach to replace scarred, non-functional myocardium in a diseased heart. At least 5--10 x 108 donor cardiomyocytes would be required for this therapy. We have developed a scalable bioprocess that can generate relatively pure cardiomyocyte cultures from differentiating mouse ES cells containing approximately 3 x 106 cardiomyocytes per 250 mL stirred suspension flask. Implementation of a bioreactor system that enables medium perfusion and direct monitoring and control of culture parameters, allowed us to investigate the effect of oxygen on in vitro cardiomyocyte development. We have data from one bioreactor run that shows, after 14 days of differentiation, a markedly higher cardiomyocyte yield under hypoxic conditions. We believe that oxygen is a bioprocess parameter that can be optimized to increase cardiomyocyte yield from differentiating ES cells. |
